Full text data of PHACTR4
PHACTR4
[Confidence: low (only semi-automatic identification from reviews)]
Phosphatase and actin regulator 4
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Phosphatase and actin regulator 4
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q8IZ21
ID PHAR4_HUMAN Reviewed; 702 AA.
AC Q8IZ21; A2APK6; B9ZVW0; D3DPM3; Q68DD4; Q6NUN6; Q8N384; Q9H395;
read moreAC Q9H6X0; Q9H8W6;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 22-JAN-2014, entry version 89.
DE RecName: Full=Phosphatase and actin regulator 4;
GN Name=PHACTR4; ORFNames=PRO2963;
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 [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 271-702 (ISOFORM 1).
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 4).
RC TISSUE=Adrenal cortex, Skin, and 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 365-702 (ISOFORM 1).
RC TISSUE=Fetal liver;
RA Zhang C., Yu Y., Zhang S., Wei H., Bi J., Zhou G., Dong C., Zai Y.,
RA Xu W., Gao F., Liu M., He F.;
RT "Functional prediction of the coding sequences of 75 new genes deduced
RT by analysis of cDNA clones from human fetal liver.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-628, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131; SER-342; SER-344;
RP THR-358; SER-427; THR-432 AND SER-628, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-628, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-118; SER-464 AND
RP SER-628, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Regulator of protein phosphatase 1 (PP1) required for
CC neural tube and optic fissure closure, and enteric neural crest
CC cell (ENCCs) migration during development. Acts as an activator of
CC PP1 by interacting with PPP1CA and preventing phosphorylation of
CC PPP1CA at 'Thr-320'. During neural tube closure, localizes to the
CC ventral neural tube and activates PP1, leading to down-regulate
CC cell proliferation within cranial neural tissue and the neural
CC retina. Also acts as a regulator of migration of enteric neural
CC crest cells (ENCCs) by activating PP1, leading to
CC dephosphorylation and subsequent activation of cofilin (COF1 or
CC COF2) and repression of the integrin signaling through the
CC RHO/ROCK pathway (By similarity).
CC -!- SUBUNIT: Binds PPP1CA and actin (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cell projection,
CC lamellipodium (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q8IZ21-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IZ21-2; Sequence=VSP_025437;
CC Name=3;
CC IsoId=Q8IZ21-3; Sequence=VSP_025436;
CC Name=4;
CC IsoId=Q8IZ21-4; Sequence=VSP_039730, VSP_039731;
CC Note=May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay;
CC -!- SIMILARITY: Belongs to the phosphatase and actin regulator family.
CC -!- SIMILARITY: Contains 3 RPEL repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG35507.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH68508.1; Type=Erroneous translation; Note=Wrong choice of CDS;
CC Sequence=BAB14483.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAB15130.1; Type=Frameshift; Positions=51;
CC Sequence=CAH18286.1; Type=Frameshift; Positions=53;
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DR EMBL; AK023233; BAB14483.1; ALT_INIT; mRNA.
DR EMBL; AK025436; BAB15130.1; ALT_FRAME; mRNA.
DR EMBL; CR749449; CAH18286.1; ALT_FRAME; mRNA.
DR EMBL; AL670471; CAM12870.1; -; Genomic_DNA.
DR EMBL; CR391992; CAM12870.1; JOINED; Genomic_DNA.
DR EMBL; AL360012; CAM12870.1; JOINED; Genomic_DNA.
DR EMBL; CR589951; CAM12871.1; -; Genomic_DNA.
DR EMBL; AL360012; CAM12871.1; JOINED; Genomic_DNA.
DR EMBL; CR391992; CAM12871.1; JOINED; Genomic_DNA.
DR EMBL; CH471059; EAX07696.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07698.1; -; Genomic_DNA.
DR EMBL; BC021247; AAH21247.3; -; mRNA.
DR EMBL; BC029266; AAH29266.1; -; mRNA.
DR EMBL; BC068508; AAH68508.1; ALT_SEQ; mRNA.
DR EMBL; AF130081; AAG35507.1; ALT_INIT; mRNA.
DR RefSeq; NP_001041648.1; NM_001048183.1.
DR RefSeq; NP_076412.3; NM_023923.3.
DR RefSeq; XP_005246028.1; XM_005245971.1.
DR RefSeq; XP_005246032.1; XM_005245975.1.
DR RefSeq; XP_005246033.1; XM_005245976.1.
DR UniGene; Hs.225641; -.
DR ProteinModelPortal; Q8IZ21; -.
DR SMR; Q8IZ21; 544-650.
DR DIP; DIP-47323N; -.
DR IntAct; Q8IZ21; 1.
DR PhosphoSite; Q8IZ21; -.
DR DMDM; 74728415; -.
DR PaxDb; Q8IZ21; -.
DR PRIDE; Q8IZ21; -.
DR DNASU; 65979; -.
DR Ensembl; ENST00000373836; ENSP00000362942; ENSG00000204138.
DR Ensembl; ENST00000373839; ENSP00000362945; ENSG00000204138.
DR GeneID; 65979; -.
DR KEGG; hsa:65979; -.
DR UCSC; uc001bpw.3; human.
DR CTD; 65979; -.
DR GeneCards; GC01P028696; -.
DR HGNC; HGNC:25793; PHACTR4.
DR HPA; HPA028985; -.
DR MIM; 608726; gene.
DR neXtProt; NX_Q8IZ21; -.
DR PharmGKB; PA134959472; -.
DR eggNOG; NOG275065; -.
DR HOVERGEN; HBG108247; -.
DR KO; K17585; -.
DR OMA; REKSTCS; -.
DR OrthoDB; EOG7QG44R; -.
DR ChiTaRS; PHACTR4; human.
DR GenomeRNAi; 65979; -.
DR NextBio; 67423; -.
DR PMAP-CutDB; Q8IZ21; -.
DR PRO; PR:Q8IZ21; -.
DR Bgee; Q8IZ21; -.
DR CleanEx; HS_PHACTR4; -.
DR Genevestigator; Q8IZ21; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0003779; F:actin binding; ISS:UniProtKB.
DR GO; GO:0008157; F:protein phosphatase 1 binding; ISS:UniProtKB.
DR GO; GO:0071862; F:protein phosphatase type 1 activator activity; ISS:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0061386; P:closure of optic fissure; ISS:UniProtKB.
DR GO; GO:0048484; P:enteric nervous system development; ISS:UniProtKB.
DR GO; GO:2001045; P:negative regulation of integrin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0001755; P:neural crest cell migration; ISS:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; ISS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0007266; P:Rho protein signal transduction; ISS:UniProtKB.
DR InterPro; IPR004018; RPEL_repeat.
DR Pfam; PF02755; RPEL; 3.
DR SMART; SM00707; RPEL; 3.
DR PROSITE; PS51073; RPEL; 3.
PE 1: Evidence at protein level;
KW Actin-binding; Alternative splicing; Cell projection;
KW Complete proteome; Cytoplasm; Developmental protein; Neurogenesis;
KW Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1 702 Phosphatase and actin regulator 4.
FT /FTId=PRO_0000287306.
FT REPEAT 63 88 RPEL 1.
FT REPEAT 583 608 RPEL 2.
FT REPEAT 621 646 RPEL 3.
FT COMPBIAS 227 433 Pro-rich.
FT COMPBIAS 478 482 Poly-Glu.
FT COMPBIAS 508 513 Poly-Glu.
FT MOD_RES 118 118 Phosphoserine.
FT MOD_RES 131 131 Phosphoserine.
FT MOD_RES 342 342 Phosphoserine.
FT MOD_RES 344 344 Phosphoserine.
FT MOD_RES 358 358 Phosphothreonine.
FT MOD_RES 427 427 Phosphoserine.
FT MOD_RES 432 432 Phosphothreonine.
FT MOD_RES 443 443 Phosphoserine (By similarity).
FT MOD_RES 464 464 Phosphoserine.
FT MOD_RES 628 628 Phosphoserine.
FT VAR_SEQ 1 16 Missing (in isoform 3).
FT /FTId=VSP_025436.
FT VAR_SEQ 1 5 MEDPF -> MGQADVSRPVNPDAV (in isoform 2).
FT /FTId=VSP_025437.
FT VAR_SEQ 6 6 E -> DFSREPWNSRGSRPAHYRARHGPGQCGSRRHNTSYQ
FT KEEQVLRLWQDLQALEMEEKKK (in isoform 4).
FT /FTId=VSP_039730.
FT VAR_SEQ 7 702 Missing (in isoform 4).
FT /FTId=VSP_039731.
FT CONFLICT 183 183 E -> G (in Ref. 2; CAH18286).
FT CONFLICT 459 459 L -> P (in Ref. 1; BAB14483).
SQ SEQUENCE 702 AA; 78211 MW; 89AC6A1D08411948 CRC64;
MEDPFEEADQ PTTEPGMVLD SVEAGDTTPP TKRKSKFSGF GKIFKPWKWR KKKSSDKFKE
TSEVLERKIS MRKPREELVK RGVLLEDPEQ GGEDPGKPSD AMLKNGHTTP IGNARSSSPV
QVEEEPVRLA SLRKAIPEED LKKRLGSTGS QPNSEAESVP ENVPKPPLLP PKRPLSSSHE
ASEGQAKDAT SSGGTARFII STSITTAPAA TTAATSLAKT VNLSVTPSPA PRTLPAAPAS
TNTTATPSLT HMVPAKQPPI PPPKPAHRNS NPVIAELSQA INSGTLLSKP SPPLPPKRGI
PSTSVPTLES AAAITTKTPS DEREKSTCSM GSELLPMISP RSPSPPLPTH IPPEPPRTPP
FPAKTFQVVP EIEFPPSLDL HQEIPQQEDQ KKEVPKRILD QNFGEPHIPS RLPPLPLHIR
IQQALTSPLP MTPILEGSHR AHSLLFENSD SFSEDSSTLG RTRSLPITIE MLKVPDDEEE
EEQTCPSTFS EEMTPTSVIP KLPQCLREEE EKESDSDSEG PIQYRDEEDE DESYQSALAN
KVKRKDTLAM KLNHRPSEPE LNLNSWPCKS KEEWNEIRHQ IGNTLIRRLS QRPTPEELEQ
RNILQPKNEA DRQAEKREIK RRLTRKLSQR PTVAELLARK ILRFNEYVEV TDAQDYDRRA
DKPWTKLTPA DKAAIRKELN EFKSSEMEVH EESKHFTRYH RP
//
ID PHAR4_HUMAN Reviewed; 702 AA.
AC Q8IZ21; A2APK6; B9ZVW0; D3DPM3; Q68DD4; Q6NUN6; Q8N384; Q9H395;
read moreAC Q9H6X0; Q9H8W6;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 22-JAN-2014, entry version 89.
DE RecName: Full=Phosphatase and actin regulator 4;
GN Name=PHACTR4; ORFNames=PRO2963;
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 [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 271-702 (ISOFORM 1).
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 4).
RC TISSUE=Adrenal cortex, Skin, and 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 365-702 (ISOFORM 1).
RC TISSUE=Fetal liver;
RA Zhang C., Yu Y., Zhang S., Wei H., Bi J., Zhou G., Dong C., Zai Y.,
RA Xu W., Gao F., Liu M., He F.;
RT "Functional prediction of the coding sequences of 75 new genes deduced
RT by analysis of cDNA clones from human fetal liver.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-628, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131; SER-342; SER-344;
RP THR-358; SER-427; THR-432 AND SER-628, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-628, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-118; SER-464 AND
RP SER-628, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Regulator of protein phosphatase 1 (PP1) required for
CC neural tube and optic fissure closure, and enteric neural crest
CC cell (ENCCs) migration during development. Acts as an activator of
CC PP1 by interacting with PPP1CA and preventing phosphorylation of
CC PPP1CA at 'Thr-320'. During neural tube closure, localizes to the
CC ventral neural tube and activates PP1, leading to down-regulate
CC cell proliferation within cranial neural tissue and the neural
CC retina. Also acts as a regulator of migration of enteric neural
CC crest cells (ENCCs) by activating PP1, leading to
CC dephosphorylation and subsequent activation of cofilin (COF1 or
CC COF2) and repression of the integrin signaling through the
CC RHO/ROCK pathway (By similarity).
CC -!- SUBUNIT: Binds PPP1CA and actin (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cell projection,
CC lamellipodium (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q8IZ21-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IZ21-2; Sequence=VSP_025437;
CC Name=3;
CC IsoId=Q8IZ21-3; Sequence=VSP_025436;
CC Name=4;
CC IsoId=Q8IZ21-4; Sequence=VSP_039730, VSP_039731;
CC Note=May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay;
CC -!- SIMILARITY: Belongs to the phosphatase and actin regulator family.
CC -!- SIMILARITY: Contains 3 RPEL repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG35507.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH68508.1; Type=Erroneous translation; Note=Wrong choice of CDS;
CC Sequence=BAB14483.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAB15130.1; Type=Frameshift; Positions=51;
CC Sequence=CAH18286.1; Type=Frameshift; Positions=53;
CC -----------------------------------------------------------------------
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DR EMBL; AK023233; BAB14483.1; ALT_INIT; mRNA.
DR EMBL; AK025436; BAB15130.1; ALT_FRAME; mRNA.
DR EMBL; CR749449; CAH18286.1; ALT_FRAME; mRNA.
DR EMBL; AL670471; CAM12870.1; -; Genomic_DNA.
DR EMBL; CR391992; CAM12870.1; JOINED; Genomic_DNA.
DR EMBL; AL360012; CAM12870.1; JOINED; Genomic_DNA.
DR EMBL; CR589951; CAM12871.1; -; Genomic_DNA.
DR EMBL; AL360012; CAM12871.1; JOINED; Genomic_DNA.
DR EMBL; CR391992; CAM12871.1; JOINED; Genomic_DNA.
DR EMBL; CH471059; EAX07696.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07698.1; -; Genomic_DNA.
DR EMBL; BC021247; AAH21247.3; -; mRNA.
DR EMBL; BC029266; AAH29266.1; -; mRNA.
DR EMBL; BC068508; AAH68508.1; ALT_SEQ; mRNA.
DR EMBL; AF130081; AAG35507.1; ALT_INIT; mRNA.
DR RefSeq; NP_001041648.1; NM_001048183.1.
DR RefSeq; NP_076412.3; NM_023923.3.
DR RefSeq; XP_005246028.1; XM_005245971.1.
DR RefSeq; XP_005246032.1; XM_005245975.1.
DR RefSeq; XP_005246033.1; XM_005245976.1.
DR UniGene; Hs.225641; -.
DR ProteinModelPortal; Q8IZ21; -.
DR SMR; Q8IZ21; 544-650.
DR DIP; DIP-47323N; -.
DR IntAct; Q8IZ21; 1.
DR PhosphoSite; Q8IZ21; -.
DR DMDM; 74728415; -.
DR PaxDb; Q8IZ21; -.
DR PRIDE; Q8IZ21; -.
DR DNASU; 65979; -.
DR Ensembl; ENST00000373836; ENSP00000362942; ENSG00000204138.
DR Ensembl; ENST00000373839; ENSP00000362945; ENSG00000204138.
DR GeneID; 65979; -.
DR KEGG; hsa:65979; -.
DR UCSC; uc001bpw.3; human.
DR CTD; 65979; -.
DR GeneCards; GC01P028696; -.
DR HGNC; HGNC:25793; PHACTR4.
DR HPA; HPA028985; -.
DR MIM; 608726; gene.
DR neXtProt; NX_Q8IZ21; -.
DR PharmGKB; PA134959472; -.
DR eggNOG; NOG275065; -.
DR HOVERGEN; HBG108247; -.
DR KO; K17585; -.
DR OMA; REKSTCS; -.
DR OrthoDB; EOG7QG44R; -.
DR ChiTaRS; PHACTR4; human.
DR GenomeRNAi; 65979; -.
DR NextBio; 67423; -.
DR PMAP-CutDB; Q8IZ21; -.
DR PRO; PR:Q8IZ21; -.
DR Bgee; Q8IZ21; -.
DR CleanEx; HS_PHACTR4; -.
DR Genevestigator; Q8IZ21; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0003779; F:actin binding; ISS:UniProtKB.
DR GO; GO:0008157; F:protein phosphatase 1 binding; ISS:UniProtKB.
DR GO; GO:0071862; F:protein phosphatase type 1 activator activity; ISS:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0061386; P:closure of optic fissure; ISS:UniProtKB.
DR GO; GO:0048484; P:enteric nervous system development; ISS:UniProtKB.
DR GO; GO:2001045; P:negative regulation of integrin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0001755; P:neural crest cell migration; ISS:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; ISS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0007266; P:Rho protein signal transduction; ISS:UniProtKB.
DR InterPro; IPR004018; RPEL_repeat.
DR Pfam; PF02755; RPEL; 3.
DR SMART; SM00707; RPEL; 3.
DR PROSITE; PS51073; RPEL; 3.
PE 1: Evidence at protein level;
KW Actin-binding; Alternative splicing; Cell projection;
KW Complete proteome; Cytoplasm; Developmental protein; Neurogenesis;
KW Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1 702 Phosphatase and actin regulator 4.
FT /FTId=PRO_0000287306.
FT REPEAT 63 88 RPEL 1.
FT REPEAT 583 608 RPEL 2.
FT REPEAT 621 646 RPEL 3.
FT COMPBIAS 227 433 Pro-rich.
FT COMPBIAS 478 482 Poly-Glu.
FT COMPBIAS 508 513 Poly-Glu.
FT MOD_RES 118 118 Phosphoserine.
FT MOD_RES 131 131 Phosphoserine.
FT MOD_RES 342 342 Phosphoserine.
FT MOD_RES 344 344 Phosphoserine.
FT MOD_RES 358 358 Phosphothreonine.
FT MOD_RES 427 427 Phosphoserine.
FT MOD_RES 432 432 Phosphothreonine.
FT MOD_RES 443 443 Phosphoserine (By similarity).
FT MOD_RES 464 464 Phosphoserine.
FT MOD_RES 628 628 Phosphoserine.
FT VAR_SEQ 1 16 Missing (in isoform 3).
FT /FTId=VSP_025436.
FT VAR_SEQ 1 5 MEDPF -> MGQADVSRPVNPDAV (in isoform 2).
FT /FTId=VSP_025437.
FT VAR_SEQ 6 6 E -> DFSREPWNSRGSRPAHYRARHGPGQCGSRRHNTSYQ
FT KEEQVLRLWQDLQALEMEEKKK (in isoform 4).
FT /FTId=VSP_039730.
FT VAR_SEQ 7 702 Missing (in isoform 4).
FT /FTId=VSP_039731.
FT CONFLICT 183 183 E -> G (in Ref. 2; CAH18286).
FT CONFLICT 459 459 L -> P (in Ref. 1; BAB14483).
SQ SEQUENCE 702 AA; 78211 MW; 89AC6A1D08411948 CRC64;
MEDPFEEADQ PTTEPGMVLD SVEAGDTTPP TKRKSKFSGF GKIFKPWKWR KKKSSDKFKE
TSEVLERKIS MRKPREELVK RGVLLEDPEQ GGEDPGKPSD AMLKNGHTTP IGNARSSSPV
QVEEEPVRLA SLRKAIPEED LKKRLGSTGS QPNSEAESVP ENVPKPPLLP PKRPLSSSHE
ASEGQAKDAT SSGGTARFII STSITTAPAA TTAATSLAKT VNLSVTPSPA PRTLPAAPAS
TNTTATPSLT HMVPAKQPPI PPPKPAHRNS NPVIAELSQA INSGTLLSKP SPPLPPKRGI
PSTSVPTLES AAAITTKTPS DEREKSTCSM GSELLPMISP RSPSPPLPTH IPPEPPRTPP
FPAKTFQVVP EIEFPPSLDL HQEIPQQEDQ KKEVPKRILD QNFGEPHIPS RLPPLPLHIR
IQQALTSPLP MTPILEGSHR AHSLLFENSD SFSEDSSTLG RTRSLPITIE MLKVPDDEEE
EEQTCPSTFS EEMTPTSVIP KLPQCLREEE EKESDSDSEG PIQYRDEEDE DESYQSALAN
KVKRKDTLAM KLNHRPSEPE LNLNSWPCKS KEEWNEIRHQ IGNTLIRRLS QRPTPEELEQ
RNILQPKNEA DRQAEKREIK RRLTRKLSQR PTVAELLARK ILRFNEYVEV TDAQDYDRRA
DKPWTKLTPA DKAAIRKELN EFKSSEMEVH EESKHFTRYH RP
//
MIM
608726
*RECORD*
*FIELD* NO
608726
*FIELD* TI
*608726 PHOSPHATASE AND ACTIN REGULATOR 4; PHACTR4
*FIELD* TX
CLONING
By searching databases for sequences similar to rat Phactr1 (608723),
read moreAllen et al. (2004) identified a family of 4 PHACTR genes in mouse and
human, including PHACTR4. The PHACTR proteins share highest similarity
in sequences surrounding the N- and C-terminal RPEL repeats and in the
C-terminal actin- and protein phosphatase-1 (PP1; see 176875)-binding
domains. In situ hybridization of rat brain showed Phactr4 highly
expressed in periventricular regions, cerebellum, and hippocampus.
GENE FUNCTION
Allen et al. (2004) determined that mouse Phactr4 coprecipitated with
both PP1 and actin following expression in human embryonic kidney cells.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PHACTR4
gene to chromosome 1 (TMAP SHGC-74491).
ANIMAL MODEL
Using N-ethyl-N-nitrosourea mutagenesis screens, Kim et al. (2007)
isolated the 'humpty dumpty' (humdy) mutant mouse line, which showed
failure to close the neural tube and optic fissure, causing exencephaly
and retinal coloboma. Homozygous humdy embryos exhibited complete
exencephaly, and most died by embryonic day 14.5, although a few
survived to birth and died shortly thereafter. About 8% of heterozygous
embryos displayed a midbrain-specific exencephaly, indicating an
incompletely penetrant dominant effect. Humdy was due to a missense
mutation in the Pp1-binding domain of Phactr4 that specifically
disrupted binding of Pp1 to Phactr4, leading to increased inhibitory
phosphorylation of thr320 on Pp1 in the ventral neural tube and eye and
disruption of Pp1 activity toward its target, Rb (RB1; 614041).
Consequently, Rb became hyperphosphorylated and inactivated, leading to
derepression of E2f (see E2F1; 189971) target genes. Loss of Phactr4
function resulted in shortening of the cell cycle, an increase in
proliferating neural progenitors, and ectopic cell division and/or cell
cycle exit defects in differentiating cells of the humdy neural tube and
retina. Loss of a single E2f1 allele rescued the exencephaly, coloboma,
and proliferation/differentiation defects of humdy mice, indicating that
the critical target of Phactr4 is the cell cycle regulator E2f1.
*FIELD* RF
1. Allen, P. B.; Greenfield, A. T.; Svenningsson, P.; Haspeslagh,
D. C.; Greengard, P.: Phactrs 1-4: a family of protein phosphatase
1 and actin regulatory proteins. Proc. Nat. Acad. Sci. 101: 7187-7192,
2004.
2. Kim, T.-H.; Goodman, J.; Anderson, K. V.; Niswander, L.: Phactr4
regulates neural tube and optic fissure closure by controlling PP1-,
Rb-, and E2F1-regulated cell-cycle progression. Dev. Cell 13: 87-102,
2007.
*FIELD* CN
Patricia A. Hartz - updated: 8/23/2007
*FIELD* CD
Patricia A. Hartz: 6/10/2004
*FIELD* ED
alopez: 06/17/2011
mgross: 8/31/2007
terry: 8/23/2007
mgross: 6/10/2004
*RECORD*
*FIELD* NO
608726
*FIELD* TI
*608726 PHOSPHATASE AND ACTIN REGULATOR 4; PHACTR4
*FIELD* TX
CLONING
By searching databases for sequences similar to rat Phactr1 (608723),
read moreAllen et al. (2004) identified a family of 4 PHACTR genes in mouse and
human, including PHACTR4. The PHACTR proteins share highest similarity
in sequences surrounding the N- and C-terminal RPEL repeats and in the
C-terminal actin- and protein phosphatase-1 (PP1; see 176875)-binding
domains. In situ hybridization of rat brain showed Phactr4 highly
expressed in periventricular regions, cerebellum, and hippocampus.
GENE FUNCTION
Allen et al. (2004) determined that mouse Phactr4 coprecipitated with
both PP1 and actin following expression in human embryonic kidney cells.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PHACTR4
gene to chromosome 1 (TMAP SHGC-74491).
ANIMAL MODEL
Using N-ethyl-N-nitrosourea mutagenesis screens, Kim et al. (2007)
isolated the 'humpty dumpty' (humdy) mutant mouse line, which showed
failure to close the neural tube and optic fissure, causing exencephaly
and retinal coloboma. Homozygous humdy embryos exhibited complete
exencephaly, and most died by embryonic day 14.5, although a few
survived to birth and died shortly thereafter. About 8% of heterozygous
embryos displayed a midbrain-specific exencephaly, indicating an
incompletely penetrant dominant effect. Humdy was due to a missense
mutation in the Pp1-binding domain of Phactr4 that specifically
disrupted binding of Pp1 to Phactr4, leading to increased inhibitory
phosphorylation of thr320 on Pp1 in the ventral neural tube and eye and
disruption of Pp1 activity toward its target, Rb (RB1; 614041).
Consequently, Rb became hyperphosphorylated and inactivated, leading to
derepression of E2f (see E2F1; 189971) target genes. Loss of Phactr4
function resulted in shortening of the cell cycle, an increase in
proliferating neural progenitors, and ectopic cell division and/or cell
cycle exit defects in differentiating cells of the humdy neural tube and
retina. Loss of a single E2f1 allele rescued the exencephaly, coloboma,
and proliferation/differentiation defects of humdy mice, indicating that
the critical target of Phactr4 is the cell cycle regulator E2f1.
*FIELD* RF
1. Allen, P. B.; Greenfield, A. T.; Svenningsson, P.; Haspeslagh,
D. C.; Greengard, P.: Phactrs 1-4: a family of protein phosphatase
1 and actin regulatory proteins. Proc. Nat. Acad. Sci. 101: 7187-7192,
2004.
2. Kim, T.-H.; Goodman, J.; Anderson, K. V.; Niswander, L.: Phactr4
regulates neural tube and optic fissure closure by controlling PP1-,
Rb-, and E2F1-regulated cell-cycle progression. Dev. Cell 13: 87-102,
2007.
*FIELD* CN
Patricia A. Hartz - updated: 8/23/2007
*FIELD* CD
Patricia A. Hartz: 6/10/2004
*FIELD* ED
alopez: 06/17/2011
mgross: 8/31/2007
terry: 8/23/2007
mgross: 6/10/2004