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Q6PJF5 (RHDF2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 88. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Inactive rhomboid protein 2

Short name=iRhom2
Alternative name(s):
Rhomboid 5 homolog 2
Rhomboid family member 2
Rhomboid veinlet-like protein 5
Rhomboid veinlet-like protein 6
Gene names
Name:RHBDF2
Synonyms:IRHOM2, RHBDL5, RHBDL6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length856 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Rhomboid protease-like protein which has no protease activity but regulates the secretion of several ligands of the epidermal growth factor receptor. Indirectly activates the epidermal growth factor receptor signaling pathway and may thereby regulate sleep, cell survival, proliferation and migration By similarity.

Subunit structure

Interacts with EGF By similarity.

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein By similarity. Cell membrane Ref.7.

Tissue specificity

Found in the epidermis and esophageal epithelium. Ref.7

Involvement in disease

Tylosis with esophageal cancer (TOC) [MIM:148500]: An autosomal dominant syndrome characterized by diffuse palmoplantar keratoderma, oral leukokeratosis, and a high lifetime risk of esophageal cancer.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Sequence similarities

Belongs to the peptidase S54 family.

Sequence caution

The sequence AAH35829.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence BAB15310.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6PJF5-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q6PJF5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     51-79: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 856856Inactive rhomboid protein 2
PRO_0000341938

Regions

Topological domain1 – 409409Cytoplasmic Potential
Transmembrane410 – 43021Helical; Potential
Topological domain431 – 660230Lumenal Potential
Transmembrane661 – 68121Helical; Potential
Topological domain682 – 69211Cytoplasmic Potential
Transmembrane693 – 71321Helical; Potential
Topological domain714 – 7152Lumenal Potential
Transmembrane716 – 73621Helical; Potential
Topological domain737 – 74711Cytoplasmic Potential
Transmembrane748 – 76821Helical; Potential
Topological domain769 – 7735Lumenal Potential
Transmembrane774 – 79421Helical; Potential
Topological domain795 – 8028Cytoplasmic Potential
Transmembrane803 – 82321Helical; Potential
Topological domain824 – 85633Lumenal Potential

Amino acid modifications

Modified residue901Phosphoserine Ref.5
Modified residue1131Phosphoserine By similarity
Modified residue1171Phosphoserine By similarity
Modified residue3231Phosphoserine By similarity
Modified residue3251Phosphoserine Ref.5
Modified residue3281Phosphoserine Ref.5

Natural variations

Alternative sequence51 – 7929Missing in isoform 2.
VSP_034368
Natural variant1861I → T in TOC. Ref.7
VAR_067827
Natural variant1891P → L in TOC. Ref.7
VAR_067828
Natural variant2081P → L. Ref.1 Ref.2 Ref.4
Corresponds to variant rs3744045 [ dbSNP | Ensembl ].
VAR_044125
Natural variant2491A → T.
Corresponds to variant rs34814954 [ dbSNP | Ensembl ].
VAR_044126
Natural variant5281D → Y.
Corresponds to variant rs11553545 [ dbSNP | Ensembl ].
VAR_044127

Experimental info

Sequence conflict671A → S in BAF84824. Ref.2
Sequence conflict671A → S in AAH16034. Ref.4
Sequence conflict7051N → D in BAF84855. Ref.2
Sequence conflict8521D → G in BAF84855. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 1, 2008. Version 2.
Checksum: 69C40A21EBDBDDC0

FASTA85696,686
        10         20         30         40         50         60 
MASADKNGGS VSSVSSSRLQ SRKPPNLSIT IPPPEKETQA PGEQDSMLPE GFQNRRLKKS 

        70         80         90        100        110        120 
QPRTWAAHTT ACPPSFLPKR KNPAYLKSVS LQEPRSRWQE SSEKRPGFRR QASLSQSIRK 

       130        140        150        160        170        180 
GAAQWFGVSG DWEGQRQQWQ RRSLHHCSMR YGRLKASCQR DLELPSQEAP SFQGTESPKP 

       190        200        210        220        230        240 
CKMPKIVDPL ARGRAFRHPE EMDRPHAPHP PLTPGVLSLT SFTSVRSGYS HLPRRKRMSV 

       250        260        270        280        290        300 
AHMSLQAAAA LLKGRSVLDA TGQRCRVVKR SFAFPSFLEE DVVDGADTFD SSFFSKEEMS 

       310        320        330        340        350        360 
SMPDDVFESP PLSASYFRGI PHSASPVSPD GVQIPLKEYG RAPVPGPRRG KRIASKVKHF 

       370        380        390        400        410        420 
AFDRKKRHYG LGVVGNWLNR SYRRSISSTV QRQLESFDSH RPYFTYWLTF VHVIITLLVI 

       430        440        450        460        470        480 
CTYGIAPVGF AQHVTTQLVL RNKGVYESVK YIQQENFWVG PSSIDLIHLG AKFSPCIRKD 

       490        500        510        520        530        540 
GQIEQLVLRE RDLERDSGCC VQNDHSGCIQ TQRKDCSETL ATFVKWQDDT GPPMDKSDLG 

       550        560        570        580        590        600 
QKRTSGAVCH QDPRTCEEPA SSGAHIWPDD ITKWPICTEQ ARSNHTGFLH MDCEIKGRPC 

       610        620        630        640        650        660 
CIGTKGSCEI TTREYCEFMH GYFHEEATLC SQVHCLDKVC GLLPFLNPEV PDQFYRLWLS 

       670        680        690        700        710        720 
LFLHAGVVHC LVSVVFQMTI LRDLEKLAGW HRIAIIFILS GITGNLASAI FLPYRAEVGP 

       730        740        750        760        770        780 
AGSQFGLLAC LFVELFQSWP LLERPWKAFL NLSAIVLFLF ICGLLPWIDN IAHIFGFLSG 

       790        800        810        820        830        840 
LLLAFAFLPY ITFGTSDKYR KRALILVSLL AFAGLFAALV LWLYIYPINW PWIEHLTCFP 

       850 
FTSRFCEKYE LDQVLH 

« Hide

Isoform 2 [UniParc].

Checksum: EEE77126D9D48F86
Show »

FASTA82793,379

References

« Hide 'large scale' references
[1]"Molecular cloning of human RHBDL5."
Kong X., Teng X., Hu L.
Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT LEU-208.
Tissue: Liver.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT LEU-208.
Tissue: Kidney epithelium, Spleen and Synovium.
[3]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT LEU-208.
Tissue: Eye and Uterus.
[5]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-90; SER-325 AND SER-328, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[6]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"RHBDF2 mutations are associated with tylosis, a familial esophageal cancer syndrome."
Blaydon D.C., Etheridge S.L., Risk J.M., Hennies H.C., Gay L.J., Carroll R., Plagnol V., McRonald F.E., Stevens H.P., Spurr N.K., Bishop D.T., Ellis A., Jankowski J., Field J.K., Leigh I.M., South A.P., Kelsell D.P.
Am. J. Hum. Genet. 90:340-346(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION, VARIANTS TOC THR-186 AND LEU-189.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY500247 mRNA. Translation: AAS77567.1.
AK025994 mRNA. Translation: BAB15310.1. Different initiation.
AK292135 mRNA. Translation: BAF84824.1.
AK292166 mRNA. Translation: BAF84855.1.
AC015802 Genomic DNA. No translation available.
BC035829 mRNA. Translation: AAH35829.1. Different initiation.
BC016034 mRNA. Translation: AAH16034.2.
CCDSCCDS32743.1. [Q6PJF5-1]
CCDS32744.1. [Q6PJF5-2]
RefSeqNP_001005498.2. NM_001005498.3. [Q6PJF5-2]
NP_078875.4. NM_024599.5. [Q6PJF5-1]
XP_005257726.1. XM_005257669.1. [Q6PJF5-1]
XP_005257727.1. XM_005257670.1. [Q6PJF5-2]
UniGeneHs.464157.

3D structure databases

ProteinModelPortalQ6PJF5.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122779. 1 interaction.

Protein family/group databases

MEROPSS54.953.

PTM databases

PhosphoSiteQ6PJF5.

Polymorphism databases

DMDM193806488.

Proteomic databases

MaxQBQ6PJF5.
PaxDbQ6PJF5.
PRIDEQ6PJF5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000313080; ENSP00000322775; ENSG00000129667. [Q6PJF5-1]
ENST00000389760; ENSP00000374410; ENSG00000129667. [Q6PJF5-2]
ENST00000591885; ENSP00000466867; ENSG00000129667. [Q6PJF5-2]
GeneID79651.
KEGGhsa:79651.
UCSCuc002jrq.2. human. [Q6PJF5-1]
uc021udh.1. human. [Q6PJF5-2]

Organism-specific databases

CTD79651.
GeneCardsGC17M074466.
HGNCHGNC:20788. RHBDF2.
HPAHPA018080.
MIM148500. phenotype.
614404. gene.
neXtProtNX_Q6PJF5.
Orphanet2198. Palmoplantar keratoderma-esophageal carcinoma syndrome.
PharmGKBPA134980674.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0705.
HOGENOMHOG000154118.
HOVERGENHBG059673.
InParanoidQ6PJF5.
OMARGIPHSA.
OrthoDBEOG7288QH.
PhylomeDBQ6PJF5.
TreeFamTF312988.

Gene expression databases

ArrayExpressQ6PJF5.
BgeeQ6PJF5.
CleanExHS_RHBDF2.
GenevestigatorQ6PJF5.

Family and domain databases

Gene3D1.20.1540.10. 2 hits.
InterProIPR002610. Peptidase_S54_rhomboid.
IPR022764. Peptidase_S54_rhomboid_dom.
IPR022241. Rhomboid_SP.
[Graphical view]
PANTHERPTHR22936. PTHR22936. 1 hit.
PfamPF01694. Rhomboid. 1 hit.
PF12595. Rhomboid_SP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiRHBDF2.
GenomeRNAi79651.
NextBio68812.
PROQ6PJF5.
SOURCESearch...

Entry information

Entry nameRHDF2_HUMAN
AccessionPrimary (citable) accession number: Q6PJF5
Secondary accession number(s): A6NEM3 expand/collapse secondary AC list , A8K801, Q5U607, Q5YGQ8, Q9H6E9
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 2008
Last sequence update: July 1, 2008
Last modified: July 9, 2014
This is version 88 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM