SRRM4_HUMAN
ID SRRM4_HUMAN Reviewed; 611 AA.
AC A7MD48; A8K5P6; B2RZH7; Q7Z5F0; Q96JH4;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2009, sequence version 2.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Serine/arginine repetitive matrix protein 4;
DE AltName: Full=Medulloblastoma antigen MU-MB-2.76;
DE AltName: Full=Neural-specific serine/arginine repetitive splicing factor of 100 kDa;
DE Short=Neural-specific SR-related protein of 100 kDa;
DE Short=nSR100;
GN Name=SRRM4; Synonyms=KIAA1853;
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 [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 522-611, AND TISSUE SPECIFICITY.
RC TISSUE=Medulloblastoma;
RX PubMed=12800201; DOI=10.1002/ijc.11208;
RA Behrends U., Schneider I., Roessler S., Frauenknecht H., Golbeck A.,
RA Lechner B., Eigenstetter G., Zobywalski C., Mueller-Weihrich S.,
RA Graubner U., Schmid I., Sackerer D., Spaeth M., Goetz C., Prantl F.,
RA Asmuss H.-P., Bise K., Mautner J.;
RT "Novel tumor antigens identified by autologous antibody screening of
RT childhood medulloblastoma cDNA libraries.";
RL Int. J. Cancer 106:244-251(2003).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=19737518; DOI=10.1016/j.cell.2009.06.012;
RA Calarco J.A., Superina S., O'Hanlon D., Gabut M., Raj B., Pan Q.,
RA Skalska U., Clarke L., Gelinas D., van der Kooy D., Zhen M., Ciruna B.,
RA Blencowe B.J.;
RT "Regulation of vertebrate nervous system alternative splicing and
RT development by an SR-related protein.";
RL Cell 138:898-910(2009).
RN [6]
RP FUNCTION.
RX PubMed=30684677; DOI=10.1016/j.neulet.2019.01.042;
RA Kawamura M., Sato S., Matsumoto G., Fukuda T., Shiba-Fukushima K., Noda S.,
RA Takanashi M., Mori N., Hattori N.;
RT "Loss of nuclear REST/NRSF in aged-dopaminergic neurons in Parkinson's
RT disease patients.";
RL Neurosci. Lett. 699:59-63(2019).
CC -!- FUNCTION: Splicing factor specifically required for neural cell
CC differentiation. Acts in conjunction with nPTB/PTBP2 by binding
CC directly to its regulated target transcripts and promotes neural-
CC specific exon inclusion in many genes that function in neural cell
CC differentiation. Required to promote the inclusion of neural-specific
CC exon 10 in nPTB/PTBP2, leading to increased expression of neural-
CC specific nPTB/PTBP2. Also promotes the inclusion of exon 16 in DAAM1 in
CC neuron extracts (By similarity). Promotes alternative splicing of REST
CC transcripts to produce REST isoform 3 (REST4) with greatly reduced
CC repressive activity, thereby activating expression of REST targets in
CC neural cells (PubMed:30684677). Plays an important role during
CC embryonic development as well as in the proper functioning of the adult
CC nervous system. Regulates alternative splicing events in genes with
CC important neuronal functions (By similarity).
CC {ECO:0000250|UniProtKB:Q8BKA3, ECO:0000269|PubMed:30684677}.
CC -!- INTERACTION:
CC A7MD48; Q02040: AKAP17A; NbExp=3; IntAct=EBI-3867173, EBI-1042725;
CC A7MD48; A0A0C4DG62: ARL6IP4; NbExp=3; IntAct=EBI-3867173, EBI-12248874;
CC A7MD48; Q6PH81: C16orf87; NbExp=3; IntAct=EBI-3867173, EBI-6598617;
CC A7MD48; Q16543: CDC37; NbExp=3; IntAct=EBI-3867173, EBI-295634;
CC A7MD48; P49759-3: CLK1; NbExp=3; IntAct=EBI-3867173, EBI-11981867;
CC A7MD48; Q9HAZ1: CLK4; NbExp=3; IntAct=EBI-3867173, EBI-633400;
CC A7MD48; Q8IZU0: FAM9B; NbExp=3; IntAct=EBI-3867173, EBI-10175124;
CC A7MD48; Q9Y383: LUC7L2; NbExp=6; IntAct=EBI-3867173, EBI-352851;
CC A7MD48; Q9P127: LUZP4; NbExp=3; IntAct=EBI-3867173, EBI-10198848;
CC A7MD48; Q96EZ8: MCRS1; NbExp=3; IntAct=EBI-3867173, EBI-348259;
CC A7MD48; Q9BU76: MMTAG2; NbExp=3; IntAct=EBI-3867173, EBI-742459;
CC A7MD48; P49756: RBM25; NbExp=3; IntAct=EBI-3867173, EBI-2211856;
CC A7MD48; Q14498: RBM39; NbExp=3; IntAct=EBI-3867173, EBI-395290;
CC A7MD48; Q9Y388: RBMX2; NbExp=3; IntAct=EBI-3867173, EBI-7704044;
CC A7MD48; Q15287: RNPS1; NbExp=3; IntAct=EBI-3867173, EBI-395959;
CC A7MD48; Q96IZ7: RSRC1; NbExp=3; IntAct=EBI-3867173, EBI-712189;
CC A7MD48; Q8TAD8: SNIP1; NbExp=6; IntAct=EBI-3867173, EBI-749336;
CC A7MD48; P08621: SNRNP70; NbExp=3; IntAct=EBI-3867173, EBI-1049228;
CC A7MD48; Q8IYB3: SRRM1; NbExp=3; IntAct=EBI-3867173, EBI-1055880;
CC A7MD48; A7MD48: SRRM4; NbExp=3; IntAct=EBI-3867173, EBI-3867173;
CC A7MD48; Q05519-2: SRSF11; NbExp=3; IntAct=EBI-3867173, EBI-11975029;
CC A7MD48; Q01081: U2AF1; NbExp=3; IntAct=EBI-3867173, EBI-632461;
CC A7MD48; P61964: WDR5; NbExp=3; IntAct=EBI-3867173, EBI-540834;
CC A7MD48; Q15973: ZNF124; NbExp=3; IntAct=EBI-3867173, EBI-2555767;
CC A7MD48; Q9HBT8: ZNF286A; NbExp=3; IntAct=EBI-3867173, EBI-10754950;
CC A7MD48; Q32M78: ZNF699; NbExp=3; IntAct=EBI-3867173, EBI-10217363;
CC A7MD48; Q15696: ZRSR2; NbExp=3; IntAct=EBI-3867173, EBI-6657923;
CC A7MD48; Q15695: ZRSR2P1; NbExp=3; IntAct=EBI-3867173, EBI-12270264;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8BKA3}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in neuronal cells (at
CC protein level). Expressed in the cerebellum.
CC {ECO:0000269|PubMed:12800201, ECO:0000269|PubMed:19737518}.
CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:Q8BKA3}.
CC -!- SIMILARITY: Belongs to the nSR100 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB47482.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB058756; BAB47482.1; ALT_INIT; mRNA.
DR EMBL; AK291361; BAF84050.1; -; mRNA.
DR EMBL; AC087885; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC084361; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC152471; AAI52472.1; -; mRNA.
DR EMBL; BC167162; AAI67162.1; -; mRNA.
DR EMBL; BC167163; AAI67163.1; -; mRNA.
DR EMBL; AY130006; AAN05090.1; -; mRNA.
DR CCDS; CCDS44994.1; -.
DR RefSeq; NP_919262.2; NM_194286.3.
DR AlphaFoldDB; A7MD48; -.
DR BioGRID; 124121; 42.
DR IntAct; A7MD48; 28.
DR STRING; 9606.ENSP00000267260; -.
DR GlyGen; A7MD48; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; A7MD48; -.
DR PhosphoSitePlus; A7MD48; -.
DR BioMuta; SRRM4; -.
DR EPD; A7MD48; -.
DR MassIVE; A7MD48; -.
DR PaxDb; A7MD48; -.
DR PeptideAtlas; A7MD48; -.
DR PRIDE; A7MD48; -.
DR ProteomicsDB; 1812; -.
DR Antibodypedia; 56195; 55 antibodies from 15 providers.
DR DNASU; 84530; -.
DR Ensembl; ENST00000267260.5; ENSP00000267260.4; ENSG00000139767.10.
DR GeneID; 84530; -.
DR KEGG; hsa:84530; -.
DR MANE-Select; ENST00000267260.5; ENSP00000267260.4; NM_194286.4; NP_919262.2.
DR CTD; 84530; -.
DR DisGeNET; 84530; -.
DR GeneCards; SRRM4; -.
DR HGNC; HGNC:29389; SRRM4.
DR HPA; ENSG00000139767; Group enriched (brain, retina).
DR MIM; 613103; gene.
DR neXtProt; NX_A7MD48; -.
DR OpenTargets; ENSG00000139767; -.
DR PharmGKB; PA165513415; -.
DR VEuPathDB; HostDB:ENSG00000139767; -.
DR eggNOG; ENOG502QSPB; Eukaryota.
DR GeneTree; ENSGT00730000111247; -.
DR HOGENOM; CLU_032561_1_0_1; -.
DR InParanoid; A7MD48; -.
DR OMA; PRTEPQN; -.
DR OrthoDB; 1260712at2759; -.
DR PhylomeDB; A7MD48; -.
DR PathwayCommons; A7MD48; -.
DR SignaLink; A7MD48; -.
DR BioGRID-ORCS; 84530; 32 hits in 1060 CRISPR screens.
DR ChiTaRS; SRRM4; human.
DR GenomeRNAi; 84530; -.
DR Pharos; A7MD48; Tbio.
DR PRO; PR:A7MD48; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; A7MD48; protein.
DR Bgee; ENSG00000139767; Expressed in cerebellar vermis and 127 other tissues.
DR ExpressionAtlas; A7MD48; baseline and differential.
DR Genevisible; A7MD48; HS.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0003729; F:mRNA binding; ISS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; ISS:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; ISS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; ISS:UniProtKB.
DR GO; GO:0042551; P:neuron maturation; IBA:GO_Central.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IDA:UniProtKB.
DR GO; GO:0043484; P:regulation of RNA splicing; ISS:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl.
DR InterPro; IPR029360; SRRM_C.
DR Pfam; PF15230; SRRM_C; 1.
PE 1: Evidence at protein level;
KW Differentiation; mRNA processing; mRNA splicing; Nucleus; Phosphoprotein;
KW Reference proteome; RNA-binding.
FT CHAIN 1..611
FT /note="Serine/arginine repetitive matrix protein 4"
FT /id="PRO_0000311911"
FT REGION 38..248
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 263..611
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 77..106
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 107..189
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 200..219
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 231..246
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 264..359
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 376..458
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 459..481
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 495..512
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 522..549
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 550..566
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 567..582
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 594..611
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 243
FT /note="S -> N (in dbSNP:rs7297606)"
FT /id="VAR_037339"
FT VARIANT 406
FT /note="R -> Q (in dbSNP:rs2723880)"
FT /id="VAR_037340"
FT VARIANT 547
FT /note="R -> S (in dbSNP:rs2555273)"
FT /id="VAR_037341"
FT CONFLICT 553
FT /note="R -> W (in Ref. 1; BAB47482 and 3; AAI52472/
FT AAI67162/AAI67163)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 611 AA; 68559 MW; 2D8B551D7C9DE43D CRC64;
MASVQQGEKQ LFEKFWRGTF KAVATPRPES IIVASITARK PLPRTEPQNN PVVPAQDGPS
EKLGQHLATE PLGTNSWERD KTCRELGATR GHSASHDKDL TPPPSSRGKK KKKKSTRKKR
RRSSSYSPSP VKKKKKKSSK KHKRRRSFSK KRRHSSSSPK SKRRDEKRHK KQSRSRPRKS
HRHRHHRCPS RSQSSESRPS SCESRHRGRS PEEGQKSRRR HSRRCSKTLC KDSPEAQSSR
PPSQPLQMLG YLSARGVITG SGSAADLFTK TASPLTTSRG RSQEYDSGND TSSPPSTQTS
SARSRGQEKG SPSGGLSKSR ELNSGNTSDS GNSFTTSSPQ NKGAMLENLS PTSRGRESRG
FQSPCLECAE VKKSSLVPST ARSSPMKGCS RSSSYASTRS SSHSSRSPNP RASPRYTQSR
STSSEKRSYS RSPSYSSKSG KRSPPSRSSR SRRSPSYSRY SPSRERDPKY SEKDSQQRER
ERARRRRRSY SPMRKRRRDS PSHLEARRIT SARKRPIPYY RPSPSSSGSL SSTSSWYSSS
SSRSASRSYS RSRSRSRSRR RSRTRTSSSS SSRSPSPGSR SRSRSRSRSR SRSRSQSRSY
SSADSYSSTR R
