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   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.
DR   Genevisible; Q9NRJ4; HS.
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
//