ID TULP4_HUMAN Reviewed; 1543 AA.
AC Q9NRJ4; Q5T3M2; Q5T3M3; Q9HD22; Q9P2F0;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 04-NOV-2008, sequence version 2.
DT 24-JAN-2024, entry version 186.
DE RecName: Full=Tubby-related protein 4;
DE AltName: Full=Tubby superfamily protein;
DE AltName: Full=Tubby-like protein 4;
GN Name=TULP4; Synonyms=KIAA1397, TUBL4, TUSP;
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] (ISOFORMS 1 AND 2), AND ALTERNATIVE SPLICING.
RC TISSUE=Brain;
RX PubMed=11595174; DOI=10.1016/s0378-1119(01)00582-0;
RA Li Q.-Z., Wang C.-Y., Shi J.-D., Ruan Q.-G., Eckenrode S.,
RA Davoodi-Semiromi A., Kukar T., Gu Y., Lian W., Wu D., She J.-X.;
RT "Molecular cloning and characterization of the mouse and human TUSP gene, a
RT novel member of the tubby superfamily.";
RL Gene 273:275-284(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI. The
RT complete sequences of 150 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-577; SER-1343 AND SER-1374,
RP AND IDENTIFICATION BY 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).
CC -!- FUNCTION: May be a substrate-recognition component of a SCF-like ECS
CC (Elongin-Cullin-SOCS-box protein) E3 ubiquitin ligase complex which
CC mediates the ubiquitination and subsequent proteasomal degradation of
CC target proteins. {ECO:0000250}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NRJ4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NRJ4-2; Sequence=VSP_006676, VSP_006677;
CC -!- TISSUE SPECIFICITY: Expressed mainly in the brain, skeletal muscle,
CC testis and kidney.
CC -!- DOMAIN: The SOCS box domain mediates the interaction with the Elongin
CC BC complex, an adapter module in different E3 ubiquitin ligase
CC complexes. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the TUB family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF87975.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA92635.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF219946; AAF87975.1; ALT_FRAME; mRNA.
DR EMBL; AF288480; AAG01020.1; -; mRNA.
DR EMBL; AB037818; BAA92635.1; ALT_INIT; mRNA.
DR EMBL; AL360169; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL353800; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW47661.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW47662.1; -; Genomic_DNA.
DR EMBL; BC152476; AAI52477.1; -; mRNA.
DR CCDS; CCDS34561.1; -. [Q9NRJ4-1]
DR CCDS; CCDS34562.1; -. [Q9NRJ4-2]
DR RefSeq; NP_001007467.1; NM_001007466.2. [Q9NRJ4-2]
DR RefSeq; NP_064630.2; NM_020245.4. [Q9NRJ4-1]
DR RefSeq; XP_016866558.1; XM_017011069.1.
DR RefSeq; XP_016866559.1; XM_017011070.1. [Q9NRJ4-1]
DR RefSeq; XP_016866560.1; XM_017011071.1.
DR AlphaFoldDB; Q9NRJ4; -.
DR SMR; Q9NRJ4; -.
DR BioGRID; 121310; 20.
DR IntAct; Q9NRJ4; 7.
DR STRING; 9606.ENSP00000356064; -.
DR GlyCosmos; Q9NRJ4; 1 site, 1 glycan.
DR GlyGen; Q9NRJ4; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q9NRJ4; -.
DR PhosphoSitePlus; Q9NRJ4; -.
DR BioMuta; TULP4; -.
DR DMDM; 212276475; -.
DR EPD; Q9NRJ4; -.
DR jPOST; Q9NRJ4; -.
DR MassIVE; Q9NRJ4; -.
DR MaxQB; Q9NRJ4; -.
DR PaxDb; 9606-ENSP00000356064; -.
DR PeptideAtlas; Q9NRJ4; -.
DR ProteomicsDB; 82378; -. [Q9NRJ4-1]
DR ProteomicsDB; 82379; -. [Q9NRJ4-2]
DR Antibodypedia; 1688; 61 antibodies from 20 providers.
DR DNASU; 56995; -.
DR Ensembl; ENST00000367094.6; ENSP00000356061.2; ENSG00000130338.13. [Q9NRJ4-2]
DR Ensembl; ENST00000367097.8; ENSP00000356064.3; ENSG00000130338.13. [Q9NRJ4-1]
DR GeneID; 56995; -.
DR KEGG; hsa:56995; -.
DR MANE-Select; ENST00000367097.8; ENSP00000356064.3; NM_020245.5; NP_064630.2.
DR UCSC; uc003qrf.4; human. [Q9NRJ4-1]
DR AGR; HGNC:15530; -.
DR CTD; 56995; -.
DR DisGeNET; 56995; -.
DR GeneCards; TULP4; -.
DR HGNC; HGNC:15530; TULP4.
DR HPA; ENSG00000130338; Low tissue specificity.
DR MIM; 619442; gene.
DR neXtProt; NX_Q9NRJ4; -.
DR OpenTargets; ENSG00000130338; -.
DR PharmGKB; PA134880863; -.
DR VEuPathDB; HostDB:ENSG00000130338; -.
DR eggNOG; KOG2503; Eukaryota.
DR GeneTree; ENSGT00940000155913; -.
DR HOGENOM; CLU_002083_1_0_1; -.
DR InParanoid; Q9NRJ4; -.
DR OMA; PPKVHSQ; -.
DR OrthoDB; 2877883at2759; -.
DR PhylomeDB; Q9NRJ4; -.
DR TreeFam; TF314076; -.
DR PathwayCommons; Q9NRJ4; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR SignaLink; Q9NRJ4; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 56995; 15 hits in 1210 CRISPR screens.
DR ChiTaRS; TULP4; human.
DR GenomeRNAi; 56995; -.
DR Pharos; Q9NRJ4; Tbio.
DR PRO; PR:Q9NRJ4; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9NRJ4; Protein.
DR Bgee; ENSG00000130338; Expressed in medial globus pallidus and 202 other cell types or tissues.
DR ExpressionAtlas; Q9NRJ4; baseline and differential.
DR Genevisible; Q9NRJ4; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1.
DR InterPro; IPR001496; SOCS_box.
DR InterPro; IPR025659; Tubby-like_C.
DR InterPro; IPR000007; Tubby_C.
DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR001680; WD40_rpt.
DR PANTHER; PTHR16517; TUBBY-RELATED; 1.
DR PANTHER; PTHR16517:SF2; TUBBY-RELATED PROTEIN 4; 1.
DR Pfam; PF07525; SOCS_box; 1.
DR Pfam; PF01167; Tub; 1.
DR SMART; SM00969; SOCS_box; 1.
DR SMART; SM00320; WD40; 2.
DR SUPFAM; SSF49842; TNF-like; 1.
DR SUPFAM; SSF54518; Tubby C-terminal domain-like; 1.
DR SUPFAM; SSF50978; WD40 repeat-like; 1.
DR PROSITE; PS50225; SOCS; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 1.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Methylation; Phosphoprotein;
KW Reference proteome; Repeat; Ubl conjugation pathway; WD repeat.
FT CHAIN 1..1543
FT /note="Tubby-related protein 4"
FT /id="PRO_0000186472"
FT REPEAT 6..72
FT /note="WD 1"
FT REPEAT 73..115
FT /note="WD 2"
FT REPEAT 116..158
FT /note="WD 3"
FT REPEAT 159..237
FT /note="WD 4"
FT REPEAT 238..276
FT /note="WD 5"
FT REPEAT 277..334
FT /note="WD 6"
FT REPEAT 335..372
FT /note="WD 7"
FT DOMAIN 364..414
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT REGION 530..577
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 829..850
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1004..1058
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1326..1355
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1367..1453
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1466..1543
FT /note="TUB"
FT COMPBIAS 1036..1058
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1329..1346
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1376..1405
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1434..1453
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 577
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 945
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL5"
FT MOD_RES 950
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL5"
FT MOD_RES 1343
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1374
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 672..678
FT /note="VTGASGV -> GDAVWTD (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10718198,
FT ECO:0000303|PubMed:11595174, ECO:0000303|PubMed:15489334"
FT /id="VSP_006676"
FT VAR_SEQ 679..1543
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10718198,
FT ECO:0000303|PubMed:11595174, ECO:0000303|PubMed:15489334"
FT /id="VSP_006677"
FT VARIANT 199
FT /note="R -> S (in dbSNP:rs705956)"
FT /id="VAR_059841"
FT VARIANT 214
FT /note="G -> S (in dbSNP:rs35262826)"
FT /id="VAR_052417"
FT VARIANT 522
FT /note="S -> N (in dbSNP:rs12206717)"
FT /id="VAR_052418"
FT VARIANT 979
FT /note="D -> N (in dbSNP:rs34622886)"
FT /id="VAR_052419"
FT VARIANT 1084
FT /note="V -> I (in dbSNP:rs34559793)"
FT /id="VAR_052420"
FT VARIANT 1281
FT /note="P -> T (in dbSNP:rs3749852)"
FT /id="VAR_052421"
FT CONFLICT 745
FT /note="P -> Q (in Ref. 1; AAF87975)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1543 AA; 169000 MW; 803AB78FF8DF2E98 CRC64;
MYAAVEHGPV LCSDSNILCL SWKGRVPKSE KEKPVCRRRY YEEGWLATGN GRGVVGVTFT
SSHCRRDRST PQRINFNLRG HNSEVVLVRW NEPYQKLATC DADGGIFVWI QYEGRWSVEL
VNDRGAQVSD FTWSHDGTQA LISYRDGFVL VGSVSGQRHW SSEINLESQI TCGIWTPDDQ
QVLFGTADGQ VIVMDCHGRM LAHVLLHESD GVLGMSWNYP IFLVEDSSES DTDSDDYAPP
QDGPAAYPIP VQNIKPLLTV SFTSGDISLM NNYDDLSPTV IRSGLKEVVA QWCTQGDLLA
VAGMERQTQL GELPNGPLLK SAMVKFYNVR GEHIFTLDTL VQRPIISICW GHRDSRLLMA
SGPALYVVRV EHRVSSLQLL CQQAIASTLR EDKDVSKLTL PPRLCSYLST AFIPTIKPPI
PDPNNMRDFV SYPSAGNERL HCTMKRTEDD PEVGGPCYTL YLEYLGGLVP ILKGRRISKL
RPEFVIMDPR TDSKPDEIYG NSLISTVIDS CNCSDSSDIE LSDDWAAKKS PKISRASKSP
KLPRISIEAR KSPKLPRAAQ ELSRSPRLPL RKPSVGSPSL TRREFPFEDI TQHNYLAQVT
SNIWGTKFKI VGLAAFLPTN LGAVIYKTSL LHLQPRQMTI YLPEVRKISM DYINLPVFNP
NVFSEDEDDL PVTGASGVPE NSPPCTVNIP IAPIHSSAQA MSPTQSIGLV QSLLANQNVQ
LDVLTNQTTA VGTAEHAGDS ATQYPVSNRY SNPGQVIFGS VEMGRIIQNP PPLSLPPPPQ
GPMQLSTVGH GDRDHEHLQK SAKALRPTPQ LAAEGDAVVF SAPQEVQVTK INPPPPYPGT
IPAAPTTAAP PPPLPPPQPP VDVCLKKGDF SLYPTSVHYQ TPLGYERITT FDSSGNVEEV
CRPRTRMLCS QNTYTLPGPG SSATLRLTAT EKKVPQPCSS ATLNRLTVPR YSIPTGDPPP
YPEIASQLAQ GRGAAQRSDN SLIHATLRRN NREATLKMAQ LADSPRAPLQ PLAKSKGGPG
GVVTQLPARP PPALYTCSQC SGTGPSSQPG ASLAHTASAS PLASQSSYSL LSPPDSARDR
TDYVNSAFTE DEALSQHCQL EKPLRHPPLP EAAVTLKRPP PYQWDPMLGE DVWVPQERTA
QTSGPNPLKL SSLMLSQGQH LDVSRLPFIS PKSPASPTAT FQTGYGMGVP YPGSYNNPPL
PGVQAPCSPK DALSPTQFAQ QEPAVVLQPL YPPSLSYCTL PPMYPGSSTC SSLQLPPVAL
HPWSSYSACP PMQNPQGTLP PKPHLVVEKP LVSPPPADLQ SHLGTEVMVE TADNFQEVLS
LTESPVPQRT EKFGKKNRKR LDSRAEEGSV QAITEGKVKK EARTLSDFNS LISSPHLGRE
KKKVKSQKDQ LKSKKLNKTN EFQDSSESEP ELFISGDELM NQSQGSRKGW KSKRSPRAAG
ELEEAKCRRA SEKEDGRLGS QGFVYVMANK QPLWNEATQV YQLDFGGRVT QESAKNFQIE
LEGRQVMQFG RIDGSAYILD FQYPFSAVQA FAVALANVTQ RLK
//
