ID   OTULL_HUMAN             Reviewed;         356 AA.
AC   Q9NUU6; Q53H50; Q9H037;
DT   06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   24-JAN-2024, entry version 132.
DE   RecName: Full=Inactive ubiquitin thioesterase OTULINL;
GN   Name=OTULINL {ECO:0000303|PubMed:31056421,
GN   ECO:0000312|HGNC:HGNC:25629};
GN   Synonyms=FAM105A {ECO:0000303|PubMed:31056421,
GN   ECO:0000312|HGNC:HGNC:25629};
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=Placenta;
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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Colon;
RA   Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA   Tanaka A., Yokoyama S.;
RL   Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Eye;
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 [LARGE SCALE MRNA] OF 239-356.
RC   TISSUE=Lymph node;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [5]
RP   LACK OF ACTIVITY.
RX   PubMed=23708998; DOI=10.1038/nature12296;
RA   Rivkin E., Almeida S.M., Ceccarelli D.F., Juang Y.C., Maclean T.A.,
RA   Srikumar T., Huang H., Dunham W.H., Fukumura R., Xie G., Gondo Y.,
RA   Raught B., Gingras A.C., Sicheri F., Cordes S.P.;
RT   "The linear ubiquitin-specific deubiquitinase gumby regulates
RT   angiogenesis.";
RL   Nature 498:318-324(2013).
RN   [6]
RP   X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS) OF 87-356, FUNCTION, SUBCELLULAR
RP   LOCATION, SUBUNIT, LACK OF ACTIVITY, DOMAIN, AND MUTAGENESIS OF
RP   2-ALA--LYS-83; ASP-139 AND HIS-352.
RX   PubMed=31056421; DOI=10.1016/j.str.2019.03.022;
RA   Ceccarelli D.F., Ivantsiv S., Mullin A.A., Coyaud E., Manczyk N.,
RA   Maisonneuve P., Kurinov I., Zhao L., Go C., Gingras A.C., Raught B.,
RA   Cordes S., Sicheri F.;
RT   "FAM105A/OTULINL Is a Pseudodeubiquitinase of the OTU-Class that Localizes
RT   to the ER Membrane.";
RL   Structure 0:0-0(2019).
CC   -!- FUNCTION: Lacks deubiquitinase activity. {ECO:0000269|PubMed:31056421}.
CC   -!- SUBUNIT: Does not bind ubiquitin or ubiquitin-like proteins.
CC       {ECO:0000269|PubMed:31056421}.
CC   -!- INTERACTION:
CC       Q9NUU6; Q13520: AQP6; NbExp=3; IntAct=EBI-6916492, EBI-13059134;
CC       Q9NUU6; Q6ZVE7: GOLT1A; NbExp=3; IntAct=EBI-6916492, EBI-17231387;
CC       Q9NUU6; Q8NBQ5: HSD17B11; NbExp=3; IntAct=EBI-6916492, EBI-1052304;
CC       Q9NUU6; O43464: HTRA2; NbExp=3; IntAct=EBI-6916492, EBI-517086;
CC       Q9NUU6; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-6916492, EBI-10266796;
CC       Q9NUU6; O14901: KLF11; NbExp=3; IntAct=EBI-6916492, EBI-948266;
CC       Q9NUU6; Q86VR2: RETREG3; NbExp=3; IntAct=EBI-6916492, EBI-10192441;
CC       Q9NUU6; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-6916492, EBI-10262251;
CC       Q9NUU6; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-6916492, EBI-8638294;
CC       Q9NUU6; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-6916492, EBI-2548832;
CC       Q9NUU6; Q9Y320: TMX2; NbExp=3; IntAct=EBI-6916492, EBI-6447886;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:31056421}.
CC       Endoplasmic reticulum membrane {ECO:0000269|PubMed:31056421};
CC       Peripheral membrane protein {ECO:0000269|PubMed:31056421}. Nucleus
CC       envelope {ECO:0000269|PubMed:31056421}.
CC   -!- DOMAIN: The N-terminal region that precedes the OTU domain mediates
CC       interaction with cellular membranes. {ECO:0000269|PubMed:31056421}.
CC   -!- SIMILARITY: Belongs to the peptidase C65 family. Otulin subfamily.
CC       {ECO:0000305}.
CC   -!- CAUTION: Although highly similar to the deubiquitinase OTULIN, lacks
CC       the conserved active site Cys at position 139 which is replaced by an
CC       Asp residue, and does not show deubiquitinase activity.
CC       {ECO:0000269|PubMed:31056421, ECO:0000305|PubMed:23708998}.
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DR   EMBL; AK001989; BAA92023.1; -; mRNA.
DR   EMBL; AK222731; BAD96451.1; -; mRNA.
DR   EMBL; BC011524; AAH11524.1; -; mRNA.
DR   EMBL; AL512750; CAC21673.1; -; mRNA.
DR   CCDS; CCDS3884.1; -.
DR   RefSeq; NP_061891.1; NM_019018.2.
DR   PDB; 6DRM; X-ray; 2.06 A; A=87-356.
DR   PDBsum; 6DRM; -.
DR   AlphaFoldDB; Q9NUU6; -.
DR   SMR; Q9NUU6; -.
DR   BioGRID; 119988; 407.
DR   IntAct; Q9NUU6; 12.
DR   STRING; 9606.ENSP00000274217; -.
DR   GlyGen; Q9NUU6; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9NUU6; -.
DR   PhosphoSitePlus; Q9NUU6; -.
DR   BioMuta; FAM105A; -.
DR   DMDM; 74734394; -.
DR   EPD; Q9NUU6; -.
DR   jPOST; Q9NUU6; -.
DR   MassIVE; Q9NUU6; -.
DR   MaxQB; Q9NUU6; -.
DR   PaxDb; 9606-ENSP00000274217; -.
DR   PeptideAtlas; Q9NUU6; -.
DR   ProteomicsDB; 82720; -.
DR   Pumba; Q9NUU6; -.
DR   Antibodypedia; 22546; 153 antibodies from 22 providers.
DR   DNASU; 54491; -.
DR   Ensembl; ENST00000274217.4; ENSP00000274217.3; ENSG00000145569.6.
DR   GeneID; 54491; -.
DR   KEGG; hsa:54491; -.
DR   MANE-Select; ENST00000274217.4; ENSP00000274217.3; NM_019018.3; NP_061891.1.
DR   UCSC; uc003jfj.4; human.
DR   AGR; HGNC:25629; -.
DR   CTD; 54491; -.
DR   DisGeNET; 54491; -.
DR   GeneCards; OTULINL; -.
DR   HGNC; HGNC:25629; OTULINL.
DR   HPA; ENSG00000145569; Tissue enhanced (bone).
DR   neXtProt; NX_Q9NUU6; -.
DR   OpenTargets; ENSG00000145569; -.
DR   PharmGKB; PA142671788; -.
DR   VEuPathDB; HostDB:ENSG00000145569; -.
DR   eggNOG; ENOG502QVY0; Eukaryota.
DR   GeneTree; ENSGT00390000009802; -.
DR   HOGENOM; CLU_051856_0_0_1; -.
DR   InParanoid; Q9NUU6; -.
DR   OMA; NDRHYHV; -.
DR   OrthoDB; 3151774at2759; -.
DR   PhylomeDB; Q9NUU6; -.
DR   TreeFam; TF328709; -.
DR   PathwayCommons; Q9NUU6; -.
DR   SignaLink; Q9NUU6; -.
DR   BioGRID-ORCS; 54491; 11 hits in 1149 CRISPR screens.
DR   ChiTaRS; FAM105A; human.
DR   GenomeRNAi; 54491; -.
DR   Pharos; Q9NUU6; Tbio.
DR   PRO; PR:Q9NUU6; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; Q9NUU6; Protein.
DR   Bgee; ENSG00000145569; Expressed in monocyte and 144 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0098554; C:cytoplasmic side of endoplasmic reticulum membrane; IDA:UniProtKB.
DR   GO; GO:0005635; C:nuclear envelope; IEA:UniProtKB-SubCell.
DR   CDD; cd22798; OTU_OTULL; 1.
DR   InterPro; IPR023235; FAM105.
DR   InterPro; IPR023236; OTULINL.
DR   PANTHER; PTHR33662:SF1; INACTIVE UBIQUITIN THIOESTERASE OTULINL; 1.
DR   PANTHER; PTHR33662; OTU DEUBIQUITINASE WITH LINEAR LINKAGE-SPECIFICITY A-RELATED; 1.
DR   Pfam; PF16218; Peptidase_C101; 1.
DR   PRINTS; PR02055; PROTEINF105.
DR   PRINTS; PR02056; PROTEINF105A.
DR   Genevisible; Q9NUU6; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Endoplasmic reticulum; Membrane; Nucleus;
KW   Reference proteome.
FT   CHAIN           1..356
FT                   /note="Inactive ubiquitin thioesterase OTULINL"
FT                   /id="PRO_0000274404"
FT   DOMAIN          128..356
FT                   /note="OTU"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00139"
FT   REGION          1..83
FT                   /note="Required for membrane binding"
FT                   /evidence="ECO:0000269|PubMed:31056421"
FT   REGION          1..22
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VARIANT         319
FT                   /note="F -> L (in dbSNP:rs16903574)"
FT                   /id="VAR_030281"
FT   MUTAGEN         2..83
FT                   /note="Missing: Loss of membrane binding."
FT                   /evidence="ECO:0000269|PubMed:31056421"
FT   MUTAGEN         139
FT                   /note="D->C: Fails to confer catalytic activity; when
FT                   associated with N-352."
FT                   /evidence="ECO:0000269|PubMed:31056421"
FT   MUTAGEN         352
FT                   /note="H->N: Fails to confer catalytic activity; when
FT                   associated with C-139."
FT                   /evidence="ECO:0000269|PubMed:31056421"
FT   CONFLICT        322
FT                   /note="N -> I (in Ref. 2; BAD96451)"
FT                   /evidence="ECO:0000305"
FT   HELIX           96..103
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   HELIX           109..125
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   STRAND          129..131
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   HELIX           139..151
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   HELIX           158..161
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   HELIX           164..166
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   HELIX           167..174
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   HELIX           177..180
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   HELIX           186..188
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   HELIX           195..214
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   HELIX           219..229
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   HELIX           233..259
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   HELIX           266..273
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   HELIX           275..277
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   HELIX           280..286
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   HELIX           288..290
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   TURN            291..293
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   HELIX           299..309
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   STRAND          312..317
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   HELIX           318..320
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   HELIX           324..326
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   STRAND          327..331
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   HELIX           334..336
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   STRAND          340..349
FT                   /evidence="ECO:0007829|PDB:6DRM"
FT   STRAND          351..355
FT                   /evidence="ECO:0007829|PDB:6DRM"
SQ   SEQUENCE   356 AA;  42196 MW;  91EEC6C877D5315B CRC64;
     MAATRSPTRA RERERSGAPA AGSDQVHSWM LATSQALDTV WRMAKGFVML AVSFLVAAIC
     YFRRLHLYSG HKLKWWIGYL QRKFKRNLSV EAEVDLLSYC AREWKGETPR NKLMRKAYEE
     LFWRHHIKCV RQVRRDNYDA LRSVLFQIFS QGISFPSWMK EKDIVKLPEK LLFSQGCNWI
     QQYSFGPEKY TGSNVFGKLR KYVELLKTQW TEFNGIRDYH KRGSMCNTLF SDAILEYKLY
     EALKFIMLYQ VTEVYEQMKT KKVIPSLFRL LFSRETSSDP LSFMMNHLNS VGDTCGLEQI
     DMFILGYSLE VKIKVFRLFK FNSRDFEVCY PEEPLRDWPE ISLLTENDRH YHIPVF
//