SSRD_HUMAN
ID SSRD_HUMAN Reviewed; 173 AA.
AC P51571; A8K378; Q53XY1;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Translocon-associated protein subunit delta;
DE Short=TRAP-delta;
DE AltName: Full=Signal sequence receptor subunit delta;
DE Short=SSR-delta;
DE Flags: Precursor;
GN Name=SSR4; Synonyms=TRAPD;
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].
RC TISSUE=Brain;
RX PubMed=7492314; DOI=10.1042/bj3120205;
RA Holthuis J.C.M., van Riel M.C.H.M., Martens G.J.M.;
RT "Translocon-associated protein TRAP delta and a novel TRAP-like protein are
RT coordinately expressed with pro-opiomelanocortin in Xenopus intermediate
RT pituitary.";
RL Biochem. J. 312:205-213(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC TISSUE=Liver, Placenta, and Spleen;
RX PubMed=9286695; DOI=10.1006/geno.1997.4822;
RA Brenner V., Nyakatura G., Rosenthal A., Platzer M.;
RT "Genomic organization of two novel genes on human Xq28: compact head to
RT head arrangement of IDH gamma and TRAP delta is conserved in rat and
RT mouse.";
RL Genomics 44:8-14(1997).
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 GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Leukocyte, 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 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 [9]
RP INVOLVEMENT IN CDG1Y.
RX PubMed=24218363; DOI=10.1093/hmg/ddt550;
RG University of Washington Center for Mendelian Genomics;
RA Losfeld M.E., Ng B.G., Kircher M., Buckingham K.J., Turner E.H.,
RA Eroshkin A., Smith J.D., Shendure J., Nickerson D.A., Bamshad M.J.,
RA Freeze H.H.;
RT "A new congenital disorder of glycosylation caused by a mutation in SSR4,
RT the signal sequence receptor 4 protein of the TRAP complex.";
RL Hum. Mol. Genet. 23:1602-1605(2014).
RN [10]
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 [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [12]
RP VARIANT ARG-144.
RX PubMed=20598277; DOI=10.1016/j.ajhg.2010.06.008;
RA Sun Y., Almomani R., Aten E., Celli J., van der Heijden J., Venselaar H.,
RA Robertson S.P., Baroncini A., Franco B., Basel-Vanagaite L., Horii E.,
RA Drut R., Ariyurek Y., den Dunnen J.T., Breuning M.H.;
RT "Terminal osseous dysplasia is caused by a single recurrent mutation in the
RT FLNA gene.";
RL Am. J. Hum. Genet. 87:146-153(2010).
CC -!- FUNCTION: TRAP proteins are part of a complex whose function is to bind
CC calcium to the ER membrane and thereby regulate the retention of ER
CC resident proteins.
CC -!- SUBUNIT: Heterotetramer of TRAP-alpha, TRAP-beta, TRAP-delta and TRAP-
CC gamma.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type
CC I membrane protein.
CC -!- DISEASE: Congenital disorder of glycosylation 1Y (CDG1Y) [MIM:300934]:
CC A form of congenital disorder of glycosylation, a multisystem disorder
CC caused by a defect in glycoprotein biosynthesis and characterized by
CC under-glycosylated serum glycoproteins. Congenital disorders of
CC glycosylation result in a wide variety of clinical features, such as
CC defects in the nervous system development, psychomotor retardation,
CC dysmorphic features, hypotonia, coagulation disorders, and
CC immunodeficiency. The broad spectrum of features reflects the critical
CC role of N-glycoproteins during embryonic development, differentiation,
CC and maintenance of cell functions. {ECO:0000269|PubMed:24218363}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the TRAP-delta family. {ECO:0000305}.
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DR EMBL; X90583; CAA62211.1; -; mRNA.
DR EMBL; Z68129; CAA92215.1; -; Genomic_DNA.
DR EMBL; Z69043; CAA93157.1; -; mRNA.
DR EMBL; BT007192; AAP35856.1; -; mRNA.
DR EMBL; AK290493; BAF83182.1; -; mRNA.
DR EMBL; U52111; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471172; EAW72811.1; -; Genomic_DNA.
DR EMBL; BC003371; AAH03371.1; -; mRNA.
DR EMBL; BC032351; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS14731.1; -.
DR PIR; S59865; S59865.
DR RefSeq; NP_001191455.1; NM_001204526.1.
DR RefSeq; NP_006271.1; NM_006280.2.
DR RefSeq; XP_011529488.1; XM_011531186.1.
DR RefSeq; XP_011529489.1; XM_011531187.1.
DR AlphaFoldDB; P51571; -.
DR BioGRID; 112626; 163.
DR CORUM; P51571; -.
DR IntAct; P51571; 65.
DR MINT; P51571; -.
DR STRING; 9606.ENSP00000317331; -.
DR ChEMBL; CHEMBL4295777; -.
DR GlyGen; P51571; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P51571; -.
DR MetOSite; P51571; -.
DR PhosphoSitePlus; P51571; -.
DR SwissPalm; P51571; -.
DR BioMuta; SSR4; -.
DR DMDM; 1711550; -.
DR EPD; P51571; -.
DR jPOST; P51571; -.
DR MassIVE; P51571; -.
DR MaxQB; P51571; -.
DR PaxDb; P51571; -.
DR PeptideAtlas; P51571; -.
DR PRIDE; P51571; -.
DR ProteomicsDB; 56334; -.
DR TopDownProteomics; P51571; -.
DR Antibodypedia; 30981; 166 antibodies from 25 providers.
DR DNASU; 6748; -.
DR Ensembl; ENST00000320857.7; ENSP00000317331.3; ENSG00000180879.14.
DR Ensembl; ENST00000370086.8; ENSP00000359103.3; ENSG00000180879.14.
DR Ensembl; ENST00000370087.5; ENSP00000359104.1; ENSG00000180879.14.
DR GeneID; 6748; -.
DR KEGG; hsa:6748; -.
DR MANE-Select; ENST00000370086.8; ENSP00000359103.3; NM_006280.3; NP_006271.1.
DR UCSC; uc004fiw.4; human.
DR CTD; 6748; -.
DR DisGeNET; 6748; -.
DR GeneCards; SSR4; -.
DR GeneReviews; SSR4; -.
DR HGNC; HGNC:11326; SSR4.
DR HPA; ENSG00000180879; Tissue enhanced (pancreas).
DR MalaCards; SSR4; -.
DR MIM; 300090; gene.
DR MIM; 300934; phenotype.
DR neXtProt; NX_P51571; -.
DR OpenTargets; ENSG00000180879; -.
DR Orphanet; 370927; SSR4-CDG.
DR PharmGKB; PA36150; -.
DR VEuPathDB; HostDB:ENSG00000180879; -.
DR eggNOG; KOG4088; Eukaryota.
DR GeneTree; ENSGT00390000008992; -.
DR HOGENOM; CLU_100264_0_1_1; -.
DR InParanoid; P51571; -.
DR OMA; GPWVNSE; -.
DR OrthoDB; 1345941at2759; -.
DR PhylomeDB; P51571; -.
DR TreeFam; TF313158; -.
DR PathwayCommons; P51571; -.
DR Reactome; R-HSA-1799339; SRP-dependent cotranslational protein targeting to membrane.
DR SignaLink; P51571; -.
DR BioGRID-ORCS; 6748; 15 hits in 698 CRISPR screens.
DR ChiTaRS; SSR4; human.
DR GeneWiki; SSR4; -.
DR GenomeRNAi; 6748; -.
DR Pharos; P51571; Tbio.
DR PRO; PR:P51571; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P51571; protein.
DR Bgee; ENSG00000180879; Expressed in pituitary gland and 206 other tissues.
DR ExpressionAtlas; P51571; baseline and differential.
DR Genevisible; P51571; HS.
DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005784; C:Sec61 translocon complex; NAS:UniProtKB.
DR InterPro; IPR008855; TRAP-delta.
DR PANTHER; PTHR12731; PTHR12731; 1.
DR Pfam; PF05404; TRAP-delta; 1.
PE 1: Evidence at protein level;
KW Congenital disorder of glycosylation; Disulfide bond;
KW Endoplasmic reticulum; Isopeptide bond; Membrane; Reference proteome;
KW Signal; Transmembrane; Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..173
FT /note="Translocon-associated protein subunit delta"
FT /id="PRO_0000033292"
FT TOPO_DOM 24..144
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 145..165
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 166..173
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DISULFID 26..57
FT /evidence="ECO:0000250"
FT CROSSLNK 73
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT VARIANT 144
FT /note="G -> R (in dbSNP:rs782018895)"
FT /evidence="ECO:0000269|PubMed:20598277"
FT /id="VAR_064161"
FT CONFLICT 109
FT /note="E -> K (in Ref. 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 173 AA; 18999 MW; 063CD2C8F6CE368B CRC64;
MAAMASLGAL ALLLLSSLSR CSAEACLEPQ ITPSYYTTSD AVISTETVFI VEISLTCKNR
VQNMALYADV GGKQFPVTRG QDVGRYQVSW SLDHKSAHAG TYEVRFFDEE SYSLLRKAQR
NNEDISIIPP LFTVSVDHRG TWNGPWVSTE VLAAAIGLVI YYLAFSAKSH IQA
