LIPA4_HUMAN
ID LIPA4_HUMAN Reviewed; 1185 AA.
AC O75335; A2RUJ5; B1APN8; B1N949; B7ZM43; O94971;
DT 16-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 19-FEB-2014, sequence version 3.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Liprin-alpha-4;
DE AltName: Full=Protein tyrosine phosphatase receptor type f polypeptide-interacting protein alpha-4;
DE Short=PTPRF-interacting protein alpha-4;
GN Name=PPFIA4; Synonyms=KIAA0897;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Spangler S.A., Hoogenraad C.C.;
RT "Characterization of liprins in the central nervous system.";
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cerebellum;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., 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., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., 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., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., 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 MRNA] (ISOFORMS 1 AND 2).
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 626-1134 (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Brain, Fetal brain, Heart, and Kidney;
RX PubMed=9624153; DOI=10.1074/jbc.273.25.15611;
RA Serra-Pages C., Medley Q.G., Tang M., Hart A., Streuli M.;
RT "Liprins, a family of LAR transmembrane protein-tyrosine phosphatase-
RT interacting proteins.";
RL J. Biol. Chem. 273:15611-15620(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 767-1185 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [7]
RP IDENTIFICATION.
RX PubMed=14612982;
RA Katoh M., Katoh M.;
RT "Identification and characterization of human PPFIA4 gene in silico.";
RL Int. J. Mol. Med. 12:1009-1014(2003).
CC -!- FUNCTION: May regulate the disassembly of focal adhesions. May localize
CC receptor-like tyrosine phosphatases type 2A at specific sites on the
CC plasma membrane, possibly regulating their interaction with the
CC extracellular environment and their association with substrates (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Forms homodimers and heterodimers with liprins-alpha and
CC liprins-beta. Interacts with the second PTPase domain of PTPRD, PTPRF
CC and PTPRS. Interacts with RIMS1 and RIMS2 (By similarity). Interacts
CC with GIT1 and GIT2 (By similarity). Interacts with GRIP1 (By
CC similarity). Interacts with KIF1A (By similarity).
CC {ECO:0000250|UniProtKB:Q91Z80}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell surface
CC {ECO:0000250}. Note=Colocalizes with PTPRF at the cell surface.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=3;
CC IsoId=O75335-3; Sequence=Displayed;
CC Name=1;
CC IsoId=O75335-1; Sequence=VSP_053668, VSP_053669;
CC Name=2;
CC IsoId=O75335-2; Sequence=VSP_053668, VSP_053669, VSP_053670;
CC -!- TISSUE SPECIFICITY: Expressed only in the heart, brain, and skeletal
CC muscle. {ECO:0000269|PubMed:9624153}.
CC -!- DOMAIN: The N-terminal coiled coil regions mediate homodimerization
CC preferentially and heterodimerization type alpha/alpha. The C-terminal,
CC non-coiled coil regions mediate heterodimerization type alpha/beta and
CC interaction with PTPRD, PTPRF and PTPRS (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the liprin family. Liprin-alpha subfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; EF428334; ABR09268.1; -; mRNA.
DR EMBL; AK126624; BAC86617.1; -; mRNA.
DR EMBL; AC096632; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC105940; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL451082; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC132923; AAI32924.1; -; mRNA.
DR EMBL; BC132925; AAI32926.1; -; mRNA.
DR EMBL; BC144262; AAI44263.1; -; mRNA.
DR EMBL; AF034801; AAC26102.1; -; mRNA.
DR EMBL; AB020704; BAA74920.1; -; mRNA.
DR RefSeq; NP_001291260.1; NM_001304331.1.
DR RefSeq; NP_001291261.1; NM_001304332.1.
DR AlphaFoldDB; O75335; -.
DR SMR; O75335; -.
DR BioGRID; 114069; 7.
DR IntAct; O75335; 4.
DR STRING; 9606.ENSP00000272198; -.
DR GlyGen; O75335; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O75335; -.
DR PhosphoSitePlus; O75335; -.
DR BioMuta; PPFIA4; -.
DR EPD; O75335; -.
DR jPOST; O75335; -.
DR MassIVE; O75335; -.
DR MaxQB; O75335; -.
DR PeptideAtlas; O75335; -.
DR PRIDE; O75335; -.
DR ProteomicsDB; 3392; -.
DR ProteomicsDB; 49906; -. [O75335-3]
DR ProteomicsDB; 49907; -. [O75335-2]
DR Antibodypedia; 34537; 42 antibodies from 16 providers.
DR DNASU; 8497; -.
DR Ensembl; ENST00000272198.10; ENSP00000272198.6; ENSG00000143847.16. [O75335-1]
DR Ensembl; ENST00000447715.6; ENSP00000402576.1; ENSG00000143847.16. [O75335-3]
DR Ensembl; ENST00000599966.5; ENSP00000471264.1; ENSG00000143847.16. [O75335-2]
DR GeneID; 8497; -.
DR KEGG; hsa:8497; -.
DR UCSC; uc001gyz.3; human. [O75335-3]
DR CTD; 8497; -.
DR DisGeNET; 8497; -.
DR GeneCards; PPFIA4; -.
DR HGNC; HGNC:9248; PPFIA4.
DR HPA; ENSG00000143847; Tissue enhanced (brain, heart muscle, skeletal muscle).
DR MIM; 603145; gene.
DR neXtProt; NX_O75335; -.
DR OpenTargets; ENSG00000143847; -.
DR PharmGKB; PA33569; -.
DR VEuPathDB; HostDB:ENSG00000143847; -.
DR eggNOG; KOG0249; Eukaryota.
DR GeneTree; ENSGT01050000244900; -.
DR HOGENOM; CLU_006923_2_0_1; -.
DR InParanoid; O75335; -.
DR OrthoDB; 440941at2759; -.
DR TreeFam; TF314207; -.
DR PathwayCommons; O75335; -.
DR Reactome; R-HSA-181429; Serotonin Neurotransmitter Release Cycle.
DR Reactome; R-HSA-181430; Norepinephrine Neurotransmitter Release Cycle.
DR Reactome; R-HSA-210500; Glutamate Neurotransmitter Release Cycle.
DR Reactome; R-HSA-212676; Dopamine Neurotransmitter Release Cycle.
DR Reactome; R-HSA-264642; Acetylcholine Neurotransmitter Release Cycle.
DR Reactome; R-HSA-388844; Receptor-type tyrosine-protein phosphatases.
DR SignaLink; O75335; -.
DR BioGRID-ORCS; 8497; 21 hits in 1081 CRISPR screens.
DR ChiTaRS; PPFIA4; human.
DR GeneWiki; PPFIA4; -.
DR GenomeRNAi; 8497; -.
DR Pharos; O75335; Tbio.
DR PRO; PR:O75335; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O75335; protein.
DR Bgee; ENSG00000143847; Expressed in cerebellar hemisphere and 128 other tissues.
DR ExpressionAtlas; O75335; baseline and differential.
DR Genevisible; O75335; HS.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0048786; C:presynaptic active zone; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; ISS:ParkinsonsUK-UCL.
DR GO; GO:0050808; P:synapse organization; IBA:GO_Central.
DR CDD; cd09562; SAM_liprin-alpha1_2_3_4_repeat1; 1.
DR CDD; cd09565; SAM_liprin-alpha1_2_3_4_repeat2; 1.
DR CDD; cd09568; SAM_liprin-alpha1_2_3_4_repeat3; 1.
DR Gene3D; 1.10.150.50; -; 3.
DR InterPro; IPR029515; Liprin.
DR InterPro; IPR037620; Liprin-alpha_SAM_rpt_1.
DR InterPro; IPR037621; Liprin-alpha_SAM_rpt_2.
DR InterPro; IPR037622; Liprin-alpha_SAM_rpt_3.
DR InterPro; IPR030439; PPFIA4.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR PANTHER; PTHR12587; PTHR12587; 1.
DR PANTHER; PTHR12587:SF5; PTHR12587:SF5; 1.
DR Pfam; PF00536; SAM_1; 2.
DR Pfam; PF07647; SAM_2; 1.
DR SMART; SM00454; SAM; 3.
DR SUPFAM; SSF47769; SSF47769; 3.
DR PROSITE; PS50105; SAM_DOMAIN; 3.
PE 2: Evidence at transcript level;
KW Alternative splicing; Coiled coil; Cytoplasm; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..1185
FT /note="Liprin-alpha-4"
FT /id="PRO_0000191032"
FT DOMAIN 829..895
FT /note="SAM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT DOMAIN 944..1008
FT /note="SAM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT DOMAIN 1032..1101
FT /note="SAM 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 638..709
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 721..757
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 24..123
FT /evidence="ECO:0000255"
FT COILED 165..499
FT /evidence="ECO:0000255"
FT COMPBIAS 638..655
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 668..696
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 725..743
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 640
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91Z80"
FT MOD_RES 681
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91Z80"
FT VAR_SEQ 1..510
FT /note="Missing (in isoform 1 and isoform 2)"
FT /evidence="ECO:0000303|PubMed:10048485,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9624153"
FT /id="VSP_053668"
FT VAR_SEQ 545..588
FT /note="LALPLTVTLRSPTWMRMSQGVCCNLEYHSSGTLCGSSGPLPVPE -> DWET
FT SPLPGMLAPAAGPAFDSDPEISDVDEDEPGGLVGSADVVSPSGHSDAQTLAMMLQEQLD
FT AINEEIR (in isoform 1 and isoform 2)"
FT /evidence="ECO:0000303|PubMed:10048485,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9624153"
FT /id="VSP_053669"
FT VAR_SEQ 928..936
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9624153"
FT /id="VSP_053670"
FT CONFLICT 803
FT /note="A -> S (in Ref. 3; AAI44263)"
FT /evidence="ECO:0000305"
FT CONFLICT 1134
FT /note="G -> A (in Ref. 5; AAC26102)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1185 AA; 134404 MW; 0DD1431820D2313E CRC64;
MCEVMPTINE GDRLGPPHGA DADANFEQLM VNMLDEREKL LESLRESQET LAATQSRLQD
AIHERDQLQR HLNSALPQEF ATLTRELSMC REQLLEREEE ISELKAERNN TRLLLEHLEC
LVSRHERSLR MTVVKRQAQS PSGVSSEVEV LKALKSLFEH HKALDEKVRE RLRAALERVT
TLEEQLAGAH QQVSALQQGA GVRDGAAEEE GTVELGPKRL WKEDTGRVEE LQELLEKQNF
ELSQARERLV TLTTTVTELE EDLGTARRDL IKSEELSSKH QRDLREALAQ KEDMEERITT
LEKRYLAAQR EATSIHDLND KLENELANKE SLHRQCEEKA RHLQELLEVA EQKLQQTMRK
AETLPEVEAE LAQRIAALTK AEERHGNIEE HLRQLEGQLE EKNQELARTA VQVRQREKMN
EDHNKRLSDT VDRLLSESNE RLQLHLKERM AALEEKNTLI QELESSQRQI EEQHHHKGRL
SEEIEKLRQE VDQLKGRGGP FVDGVHSRSH MGSAADVRFS LGTTTHAPPG VHRRYSALRE
ESAKLALPLT VTLRSPTWMR MSQGVCCNLE YHSSGTLCGS SGPLPVPEMI QEEKESTELR
AEEIETRVTS GSMEALNLKQ LRKRGSIPTS LTALSLASAS PPLSGRSTPK LTSRSAAQDL
DRMGVMTLPS DLRKHRRKLL SPVSREENRE DKATIKCETS PPSSPRTLRL EKLGHPALSQ
EEGKSALEDQ GSNPSSSNSS QDSLHKGAKR KGIKSSIGRL FGKKEKGRLI QLSRDGATGH
VLLTDSEFSM QEPMVPAKLG TQAEKDRRLK KKHQLLEDAR RKGMPFAQWD GPTVVSWLEL
WVGMPAWYVA ACRANVKSGA IMSALSDTEI QREIGISNAL HRLKLRLAIQ EMVSLTSPSA
PPTSRTSSGN VWVTHEEMET LETSTKTDSE EGSWAQTLAY GDMNHEWIGN EWLPSLGLPQ
YRSYFMECLV DARMLDHLTK KDLRVHLKMV DSFHRTSLQY GIMCLKRLNY DRKELEKRRE
ESQHEIKDVL VWTNDQVVHW VQSIGLRDYA GNLHESGVHG ALLALDENFD HNTLALILQI
PTQNTQARQV MEREFNNLLA LGTDRKLDDG DDKVFRRAPS WRKRFRPREH HGRGGMLSAS
AETLPAGFRV STLGTLQPPP APPKKIMPEA HSHYLYGHML SAFRD
