PROF1_HUMAN
ID PROF1_HUMAN Reviewed; 140 AA.
AC P07737; Q53Y44;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 231.
DE RecName: Full=Profilin-1;
DE AltName: Full=Epididymis tissue protein Li 184a;
DE AltName: Full=Profilin I;
GN Name=PFN1;
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].
RX PubMed=3356709; DOI=10.1016/s0021-9258(18)60651-9;
RA Kwiatkowski D.J., Bruns G.A.P.;
RT "Human profilin. Molecular cloning, sequence comparison, and chromosomal
RT analysis.";
RL J. Biol. Chem. 263:5910-5915(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Epididymis;
RX PubMed=20736409; DOI=10.1074/mcp.m110.001719;
RA Li J., Liu F., Wang H., Liu X., Liu J., Li N., Wan F., Wang W., Zhang C.,
RA Jin S., Liu J., Zhu P., Liu Y.;
RT "Systematic mapping and functional analysis of a family of human epididymal
RT secretory sperm-located proteins.";
RL Mol. Cell. Proteomics 9:2517-2528(2010).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon, Lung, Pancreas, and Placenta;
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 [8]
RP PROTEIN SEQUENCE OF 2-140, AND ACETYLATION AT ALA-2.
RX PubMed=3342873; DOI=10.1016/0014-5793(88)80575-1;
RA Ampe C., Markey F., Lindberg U., Vandekerckhove J.;
RT "The primary structure of human platelet profilin: reinvestigation of the
RT calf spleen profilin sequence.";
RL FEBS Lett. 228:17-21(1988).
RN [9]
RP CHARACTERIZATION.
RX PubMed=7758455; DOI=10.1111/j.1432-1033.1995.tb20506.x;
RA Gieselmann R., Kwiatkowski D.J., Janmey P.A., Witke W.;
RT "Distinct biochemical characteristics of the two human profilin isoforms.";
RL Eur. J. Biochem. 229:621-628(1995).
RN [10]
RP IDENTIFICATION IN A COMPLEX WITH RAN; ACTB AND XPO6.
RX PubMed=14592989; DOI=10.1093/emboj/cdg565;
RA Stueven T., Hartmann E., Goerlich D.;
RT "Exportin 6: a novel nuclear export receptor that is specific for
RT profilin.actin complexes.";
RL EMBO J. 22:5928-5940(2003).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-129, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [13]
RP FUNCTION, INTERACTION WITH HTT, AND PHOSPHORYLATION AT SER-138.
RX PubMed=18573880; DOI=10.1128/mcb.00079-08;
RA Shao J., Welch W.J., Diprospero N.A., Diamond M.I.;
RT "Phosphorylation of profilin by ROCK1 regulates polyglutamine
RT aggregation.";
RL Mol. Cell. Biol. 28:5196-5208(2008).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85, AND IDENTIFICATION BY
RP 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 [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-105 AND LYS-108, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [17]
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., Buerckstuemmer T.,
RA 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 [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22905912; DOI=10.1021/pr300539b;
RA Rosenow A., Noben J.P., Jocken J., Kallendrusch S., Fischer-Posovszky P.,
RA Mariman E.C., Renes J.;
RT "Resveratrol-induced changes of the human adipocyte secretion profile.";
RL J. Proteome Res. 11:4733-4743(2012).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-57, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [23]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-54, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [24]
RP STRUCTURE BY NMR.
RX PubMed=8268157; DOI=10.1021/bi00213a010;
RA Metzler W.J., Constantine K.L., Friedrichs M.S., Bell A.J., Ernst E.G.,
RA Lavoie T.B., Mueller L.;
RT "Characterization of the three-dimensional solution structure of human
RT profilin: 1H, 13C, and 15N NMR assignments and global folding pattern.";
RL Biochemistry 32:13818-13829(1993).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
RA Fedorov A.A., Pollard T.D., Almo S.C.;
RL Submitted (APR-1996) to the PDB data bank.
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF COMPLEX WITH POLY-PRO.
RX PubMed=9360613; DOI=10.1038/nsb1197-953;
RA Mahoney N.M., Janmey P.A., Almo S.C.;
RT "Structure of the profilin-poly-L-proline complex involved in morphogenesis
RT and cytoskeletal regulation.";
RL Nat. Struct. Biol. 4:953-960(1997).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF COMPLEX WITH POLY-PRO.
RX PubMed=10404225; DOI=10.1038/10722;
RA Mahoney N.M., Rozwarski D.A., Fedorov E., Fedorov A.A., Almo S.C.;
RT "Profilin binds proline-rich ligands in two distinct amide backbone
RT orientations.";
RL Nat. Struct. Biol. 6:666-671(1999).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 2-140 IN COMPLEXES WITH VASP AND
RP MONOMERIC ACTIN, AND INTERACTION WITH VASP.
RX PubMed=17914456; DOI=10.1038/sj.emboj.7601874;
RA Ferron F., Rebowski G., Lee S.H., Dominguez R.;
RT "Structural basis for the recruitment of profilin-actin complexes during
RT filament elongation by Ena/VASP.";
RL EMBO J. 26:4597-4606(2007).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 2-140 IN COMPLEX WITH VASP AND
RP ACTIN.
RX PubMed=18689676; DOI=10.1073/pnas.0805852105;
RA Baek K., Liu X., Ferron F., Shu S., Korn E.D., Dominguez R.;
RT "Modulation of actin structure and function by phosphorylation of Tyr-53
RT and profilin binding.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:11748-11753(2008).
RN [30]
RP VARIANTS ALS18 GLY-71; THR-114; GLY-117 AND VAL-118, AND CHARACTERIZATION
RP OF VARIANTS ALS18 GLY-71; THR-114; GLY-117 AND VAL-118.
RX PubMed=22801503; DOI=10.1038/nature11280;
RA Wu C.H., Fallini C., Ticozzi N., Keagle P.J., Sapp P.C., Piotrowska K.,
RA Lowe P., Koppers M., McKenna-Yasek D., Baron D.M., Kost J.E.,
RA Gonzalez-Perez P., Fox A.D., Adams J., Taroni F., Tiloca C., Leclerc A.L.,
RA Chafe S.C., Mangroo D., Moore M.J., Zitzewitz J.A., Xu Z.S.,
RA van den Berg L.H., Glass J.D., Siciliano G., Cirulli E.T., Goldstein D.B.,
RA Salachas F., Meininger V., Rossoll W., Ratti A., Gellera C., Bosco D.A.,
RA Bassell G.J., Silani V., Drory V.E., Brown R.H. Jr., Landers J.E.;
RT "Mutations in the profilin 1 gene cause familial amyotrophic lateral
RT sclerosis.";
RL Nature 488:499-503(2012).
CC -!- FUNCTION: Binds to actin and affects the structure of the cytoskeleton.
CC At high concentrations, profilin prevents the polymerization of actin,
CC whereas it enhances it at low concentrations. By binding to PIP2, it
CC inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR)
CC and HTT aggregation and binding of G-actin is essential for its
CC inhibition of AR. {ECO:0000269|PubMed:18573880}.
CC -!- SUBUNIT: Occurs in many kinds of cells as a complex with monomeric
CC actin in a 1:1 ratio. Found in a complex with XPO6, Ran, ACTB and PFN1.
CC Interacts with VASP. Interacts with HTT. {ECO:0000269|PubMed:14592989,
CC ECO:0000269|PubMed:17914456, ECO:0000269|PubMed:18573880,
CC ECO:0000269|PubMed:18689676}.
CC -!- INTERACTION:
CC P07737; P60709: ACTB; NbExp=2; IntAct=EBI-713780, EBI-353944;
CC P07737; Q92558: WASF1; NbExp=2; IntAct=EBI-713780, EBI-1548747;
CC P07737; P07830: act21; Xeno; NbExp=3; IntAct=EBI-713780, EBI-7195234;
CC P07737; P68135: ACTA1; Xeno; NbExp=2; IntAct=EBI-713780, EBI-367540;
CC P07737; O08816: Wasl; Xeno; NbExp=4; IntAct=EBI-713780, EBI-6142604;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
CC -!- TISSUE SPECIFICITY: Expressed in epididymis (at protein level).
CC {ECO:0000269|PubMed:20736409}.
CC -!- PTM: Phosphorylation at Ser-138 reduces its affinity for G-actin and
CC blocks its interaction with HTT, reducing its ability to inhibit
CC androgen receptor (AR) and HTT aggregation.
CC {ECO:0000269|PubMed:18573880}.
CC -!- DISEASE: Amyotrophic lateral sclerosis 18 (ALS18) [MIM:614808]: A
CC neurodegenerative disorder affecting upper motor neurons in the brain
CC and lower motor neurons in the brain stem and spinal cord, resulting in
CC fatal paralysis. Sensory abnormalities are absent. The pathologic
CC hallmarks of the disease include pallor of the corticospinal tract due
CC to loss of motor neurons, presence of ubiquitin-positive inclusions
CC within surviving motor neurons, and deposition of pathologic
CC aggregates. The etiology of amyotrophic lateral sclerosis is likely to
CC be multifactorial, involving both genetic and environmental factors.
CC The disease is inherited in 5-10% of the cases.
CC {ECO:0000269|PubMed:22801503}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the profilin family. {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; J03191; AAA36486.1; -; mRNA.
DR EMBL; GU727630; ADU87632.1; -; mRNA.
DR EMBL; BT007001; AAP35647.1; -; mRNA.
DR EMBL; AK312168; BAG35102.1; -; mRNA.
DR EMBL; CR407670; CAG28598.1; -; mRNA.
DR EMBL; CH471108; EAW90381.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90383.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90384.1; -; Genomic_DNA.
DR EMBL; BC002475; AAH02475.1; -; mRNA.
DR EMBL; BC006768; AAH06768.1; -; mRNA.
DR EMBL; BC013439; AAH13439.1; -; mRNA.
DR EMBL; BC015164; AAH15164.1; -; mRNA.
DR EMBL; BC057828; AAH57828.1; -; mRNA.
DR CCDS; CCDS11061.1; -.
DR PIR; A28622; A28622.
DR RefSeq; NP_005013.1; NM_005022.3.
DR PDB; 1AWI; X-ray; 2.20 A; A/B=3-140.
DR PDB; 1CF0; X-ray; 2.20 A; A/B=3-140.
DR PDB; 1CJF; X-ray; 2.30 A; A/B=2-140.
DR PDB; 1FIK; X-ray; 2.30 A; A=2-140.
DR PDB; 1FIL; X-ray; 2.00 A; A=2-140.
DR PDB; 1PFL; NMR; -; A=2-140.
DR PDB; 2PAV; X-ray; 1.80 A; P=2-140.
DR PDB; 2PBD; X-ray; 1.50 A; P=2-140.
DR PDB; 3CHW; X-ray; 2.30 A; P=2-140.
DR PDB; 4X1L; X-ray; 2.16 A; A=1-140.
DR PDB; 4X1M; X-ray; 2.17 A; A=1-140.
DR PDB; 4X25; X-ray; 2.23 A; A/B=1-140.
DR PDB; 6NAS; X-ray; 2.90 A; P=1-140.
DR PDB; 6NBE; X-ray; 2.00 A; P=1-140.
DR PDB; 6NBW; X-ray; 2.50 A; P=1-140.
DR PDB; 7P1H; EM; 3.90 A; P=1-140.
DR PDBsum; 1AWI; -.
DR PDBsum; 1CF0; -.
DR PDBsum; 1CJF; -.
DR PDBsum; 1FIK; -.
DR PDBsum; 1FIL; -.
DR PDBsum; 1PFL; -.
DR PDBsum; 2PAV; -.
DR PDBsum; 2PBD; -.
DR PDBsum; 3CHW; -.
DR PDBsum; 4X1L; -.
DR PDBsum; 4X1M; -.
DR PDBsum; 4X25; -.
DR PDBsum; 6NAS; -.
DR PDBsum; 6NBE; -.
DR PDBsum; 6NBW; -.
DR PDBsum; 7P1H; -.
DR AlphaFoldDB; P07737; -.
DR BMRB; P07737; -.
DR SMR; P07737; -.
DR BioGRID; 111237; 380.
DR CORUM; P07737; -.
DR DIP; DIP-30N; -.
DR IntAct; P07737; 79.
DR MINT; P07737; -.
DR STRING; 9606.ENSP00000225655; -.
DR DrugBank; DB07908; 7-HYDROXY-4-METHYL-3-(2-HYDROXY-ETHYL)COUMARIN.
DR DrugBank; DB11638; Artenimol.
DR Allergome; 907; Hom s Profilin.
DR GlyGen; P07737; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P07737; -.
DR MetOSite; P07737; -.
DR PhosphoSitePlus; P07737; -.
DR SwissPalm; P07737; -.
DR BioMuta; PFN1; -.
DR DMDM; 130979; -.
DR DOSAC-COBS-2DPAGE; P07737; -.
DR OGP; P07737; -.
DR REPRODUCTION-2DPAGE; IPI00216691; -.
DR UCD-2DPAGE; P07737; -.
DR CPTAC; CPTAC-253; -.
DR CPTAC; CPTAC-254; -.
DR EPD; P07737; -.
DR jPOST; P07737; -.
DR MassIVE; P07737; -.
DR PaxDb; P07737; -.
DR PeptideAtlas; P07737; -.
DR PRIDE; P07737; -.
DR ProteomicsDB; 52024; -.
DR TopDownProteomics; P07737; -.
DR Antibodypedia; 23487; 454 antibodies from 35 providers.
DR DNASU; 5216; -.
DR Ensembl; ENST00000225655.6; ENSP00000225655.5; ENSG00000108518.8.
DR GeneID; 5216; -.
DR KEGG; hsa:5216; -.
DR MANE-Select; ENST00000225655.6; ENSP00000225655.5; NM_005022.4; NP_005013.1.
DR UCSC; uc002gaa.5; human.
DR CTD; 5216; -.
DR DisGeNET; 5216; -.
DR GeneCards; PFN1; -.
DR HGNC; HGNC:8881; PFN1.
DR HPA; ENSG00000108518; Low tissue specificity.
DR MalaCards; PFN1; -.
DR MIM; 176610; gene.
DR MIM; 614808; phenotype.
DR neXtProt; NX_P07737; -.
DR OpenTargets; ENSG00000108518; -.
DR Orphanet; 803; Amyotrophic lateral sclerosis.
DR PharmGKB; PA33219; -.
DR VEuPathDB; HostDB:ENSG00000108518; -.
DR eggNOG; KOG1755; Eukaryota.
DR GeneTree; ENSGT00940000153664; -.
DR HOGENOM; CLU_123405_1_0_1; -.
DR InParanoid; P07737; -.
DR OMA; NKKCFEM; -.
DR OrthoDB; 1428600at2759; -.
DR PhylomeDB; P07737; -.
DR TreeFam; TF331744; -.
DR PathwayCommons; P07737; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR Reactome; R-HSA-376176; Signaling by ROBO receptors.
DR Reactome; R-HSA-4086400; PCP/CE pathway.
DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins.
DR SignaLink; P07737; -.
DR SIGNOR; P07737; -.
DR BioGRID-ORCS; 5216; 588 hits in 1087 CRISPR screens.
DR ChiTaRS; PFN1; human.
DR EvolutionaryTrace; P07737; -.
DR GeneWiki; Profilin_1; -.
DR GenomeRNAi; 5216; -.
DR Pharos; P07737; Tbio.
DR PRO; PR:P07737; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P07737; protein.
DR Bgee; ENSG00000108518; Expressed in granulocyte and 207 other tissues.
DR ExpressionAtlas; P07737; baseline and differential.
DR Genevisible; P07737; HS.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; IPI:UniProtKB.
DR GO; GO:0003785; F:actin monomer binding; IDA:UniProtKB.
DR GO; GO:0000774; F:adenyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IPI:UniProtKB.
DR GO; GO:0070064; F:proline-rich region binding; IPI:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl.
DR GO; GO:0030036; P:actin cytoskeleton organization; IEA:InterPro.
DR GO; GO:0098885; P:modification of postsynaptic actin cytoskeleton; IEA:Ensembl.
DR GO; GO:0032232; P:negative regulation of actin filament bundle assembly; IMP:UniProtKB.
DR GO; GO:0030837; P:negative regulation of actin filament polymerization; IDA:UniProtKB.
DR GO; GO:0051497; P:negative regulation of stress fiber assembly; IMP:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:0032233; P:positive regulation of actin filament bundle assembly; IBA:GO_Central.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IGI:UniProtKB.
DR GO; GO:0032781; P:positive regulation of ATP-dependent activity; IDA:UniProtKB.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; IMP:UniProtKB.
DR GO; GO:1900029; P:positive regulation of ruffle assembly; IMP:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB.
DR GO; GO:0030833; P:regulation of actin filament polymerization; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0060074; P:synapse maturation; IEA:Ensembl.
DR CDD; cd00148; PROF; 1.
DR InterPro; IPR005455; PFN.
DR InterPro; IPR029892; PFN1.
DR InterPro; IPR036140; PFN_sf.
DR InterPro; IPR005454; Profilin1/2/3_vertebrate.
DR InterPro; IPR027310; Profilin_CS.
DR PANTHER; PTHR13936:SF14; PTHR13936:SF14; 1.
DR Pfam; PF00235; Profilin; 1.
DR PRINTS; PR01639; PROFILINMAML.
DR SMART; SM00392; PROF; 1.
DR SUPFAM; SSF55770; SSF55770; 1.
DR PROSITE; PS00414; PROFILIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin-binding; Amyotrophic lateral sclerosis;
KW Cytoplasm; Cytoskeleton; Direct protein sequencing; Disease variant;
KW Isopeptide bond; Neurodegeneration; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:3342873,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:25944712"
FT CHAIN 2..140
FT /note="Profilin-1"
FT /id="PRO_0000199571"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:3342873,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:25944712"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62963"
FT MOD_RES 57
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 105
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 108
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 129
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 138
FT /note="Phosphoserine; by ROCK1"
FT /evidence="ECO:0000269|PubMed:18573880"
FT CROSSLNK 54
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 54
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT VARIANT 71
FT /note="C -> G (in ALS18; the mutant protein is detected in
FT the insoluble fraction of cells; dbSNP:rs387907264)"
FT /evidence="ECO:0000269|PubMed:22801503"
FT /id="VAR_068925"
FT VARIANT 114
FT /note="M -> T (in ALS18; the mutant protein is detected in
FT the insoluble fraction of cells; dbSNP:rs387907265)"
FT /evidence="ECO:0000269|PubMed:22801503"
FT /id="VAR_068926"
FT VARIANT 117
FT /note="E -> G (in ALS18; unknown pathological significance;
FT like the wild-type the mutant protein is detected in the
FT soluble fraction of cells; dbSNP:rs140547520)"
FT /evidence="ECO:0000269|PubMed:22801503"
FT /id="VAR_068927"
FT VARIANT 118
FT /note="G -> V (in ALS18; the mutant protein is detected in
FT the insoluble fraction of cells; dbSNP:rs387907266)"
FT /evidence="ECO:0000269|PubMed:22801503"
FT /id="VAR_068928"
FT HELIX 5..12
FT /evidence="ECO:0007829|PDB:2PBD"
FT STRAND 13..15
FT /evidence="ECO:0007829|PDB:4X1L"
FT STRAND 17..28
FT /evidence="ECO:0007829|PDB:2PBD"
FT STRAND 30..34
FT /evidence="ECO:0007829|PDB:2PBD"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:2PBD"
FT HELIX 45..52
FT /evidence="ECO:0007829|PDB:2PBD"
FT HELIX 58..60
FT /evidence="ECO:0007829|PDB:2PBD"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:2PBD"
FT STRAND 69..77
FT /evidence="ECO:0007829|PDB:2PBD"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:1FIL"
FT TURN 81..83
FT /evidence="ECO:0007829|PDB:2PBD"
FT STRAND 85..90
FT /evidence="ECO:0007829|PDB:2PBD"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:1AWI"
FT STRAND 100..105
FT /evidence="ECO:0007829|PDB:2PBD"
FT STRAND 107..115
FT /evidence="ECO:0007829|PDB:2PBD"
FT HELIX 121..137
FT /evidence="ECO:0007829|PDB:2PBD"
SQ SEQUENCE 140 AA; 15054 MW; F725119E55A289EB CRC64;
MAGWNAYIDN LMADGTCQDA AIVGYKDSPS VWAAVPGKTF VNITPAEVGV LVGKDRSSFY
VNGLTLGGQK CSVIRDSLLQ DGEFSMDLRT KSTGGAPTFN VTVTKTDKTL VLLMGKEGVH
GGLINKKCYE MASHLRRSQY
