Q6PJF5 (RHDF2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	856 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cell membrane Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Palmoplantar keratoderma
Domain	Transmembrane Transmembrane helix
Ligand	Growth factor binding
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of protein secretion Inferred from sequence or structural similarity. Source: UniProtKB protein transport Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: InterPro
Cellular_component	endoplasmic reticulum membrane Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 856	856	Inactive rhomboid protein 2		PRO_0000341938
Regions
	Topological domain	1 – 409	409	Cytoplasmic Potential
	Transmembrane	410 – 430	21	Helical; Potential
	Topological domain	431 – 660	230	Lumenal Potential
	Transmembrane	661 – 681	21	Helical; Potential
	Topological domain	682 – 692	11	Cytoplasmic Potential
	Transmembrane	693 – 713	21	Helical; Potential
	Topological domain	714 – 715	2	Lumenal Potential
	Transmembrane	716 – 736	21	Helical; Potential
	Topological domain	737 – 747	11	Cytoplasmic Potential
	Transmembrane	748 – 768	21	Helical; Potential
	Topological domain	769 – 773	5	Lumenal Potential
	Transmembrane	774 – 794	21	Helical; Potential
	Topological domain	795 – 802	8	Cytoplasmic Potential
	Transmembrane	803 – 823	21	Helical; Potential
	Topological domain	824 – 856	33	Lumenal Potential
Amino acid modifications
	Modified residue	90	1	Phosphoserine Ref.5
	Modified residue	113	1	Phosphoserine By similarity
	Modified residue	117	1	Phosphoserine By similarity
	Modified residue	323	1	Phosphoserine By similarity
	Modified residue	325	1	Phosphoserine Ref.5
	Modified residue	328	1	Phosphoserine Ref.5
	Modified residue	387	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	51 – 79	29	Missing in isoform 2.		VSP_034368
	Natural variant	186	1	I → T in TOC. Ref.7		VAR_067827
	Natural variant	189	1	P → L in TOC. Ref.7		VAR_067828
	Natural variant	208	1	P → L. Ref.1 Ref.2 Ref.4 Corresponds to variant rs3744045 [ dbSNP | Ensembl ].		VAR_044125
	Natural variant	249	1	A → T. Corresponds to variant rs34814954 [ dbSNP | Ensembl ].		VAR_044126
	Natural variant	528	1	D → Y. Corresponds to variant rs11553545 [ dbSNP | Ensembl ].		VAR_044127
Experimental info
	Sequence conflict	67	1	A → S in BAF84824. Ref.2
	Sequence conflict	67	1	A → S in AAH16034. Ref.4
	Sequence conflict	705	1	N → D in BAF84855. Ref.2
	Sequence conflict	852	1	D → G in BAF84855. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 1, 2008. Version 2. Checksum: 69C40A21EBDBDDC0	FASTA	856	96,686
	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
	Isoform 2 [UniParc]. Checksum: EEE77126D9D48F86	FASTA	827	93,379
	10 20 30 40 50 60 MASADKNGGS VSSVSSSRLQ SRKPPNLSIT IPPPEKETQA PGEQDSMLPE RKNPAYLKSV 70 80 90 100 110 120 SLQEPRSRWQ ESSEKRPGFR RQASLSQSIR KGAAQWFGVS GDWEGQRQQW QRRSLHHCSM 130 140 150 160 170 180 RYGRLKASCQ RDLELPSQEA PSFQGTESPK PCKMPKIVDP LARGRAFRHP EEMDRPHAPH 190 200 210 220 230 240 PPLTPGVLSL TSFTSVRSGY SHLPRRKRMS VAHMSLQAAA ALLKGRSVLD ATGQRCRVVK 250 260 270 280 290 300 RSFAFPSFLE EDVVDGADTF DSSFFSKEEM SSMPDDVFES PPLSASYFRG IPHSASPVSP 310 320 330 340 350 360 DGVQIPLKEY GRAPVPGPRR GKRIASKVKH FAFDRKKRHY GLGVVGNWLN RSYRRSISST 370 380 390 400 410 420 VQRQLESFDS HRPYFTYWLT FVHVIITLLV ICTYGIAPVG FAQHVTTQLV LRNKGVYESV 430 440 450 460 470 480 KYIQQENFWV GPSSIDLIHL GAKFSPCIRK DGQIEQLVLR ERDLERDSGC CVQNDHSGCI 490 500 510 520 530 540 QTQRKDCSET LATFVKWQDD TGPPMDKSDL GQKRTSGAVC HQDPRTCEEP ASSGAHIWPD 550 560 570 580 590 600 DITKWPICTE QARSNHTGFL HMDCEIKGRP CCIGTKGSCE ITTREYCEFM HGYFHEEATL 610 620 630 640 650 660 CSQVHCLDKV CGLLPFLNPE VPDQFYRLWL SLFLHAGVVH CLVSVVFQMT ILRDLEKLAG 670 680 690 700 710 720 WHRIAIIFIL SGITGNLASA IFLPYRAEVG PAGSQFGLLA CLFVELFQSW PLLERPWKAF 730 740 750 760 770 780 LNLSAIVLFL FICGLLPWID NIAHIFGFLS GLLLAFAFLP YITFGTSDKY RKRALILVSL 790 800 810 820 LAFAGLFAAL VLWLYIYPIN WPWIEHLTCF PFTSRFCEKY ELDQVLH

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. 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.
IPI	IPI00433499. IPI00470604.
RefSeq	NP_001005498.2. NM_001005498.3. NP_078875.4. NM_024599.5.
UniGene	Hs.464157.
3D structure databases
ProteinModelPortal	Q6PJF5.
ModBase	Search...
Protein family/group databases
MEROPS	S54.953.
PTM databases
PhosphoSite	Q6PJF5.
Polymorphism databases
DMDM	193806488.
Proteomic databases
PaxDb	Q6PJF5.
PRIDE	Q6PJF5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000313080; ENSP00000322775; ENSG00000129667. ENST00000389760; ENSP00000374410; ENSG00000129667. ENST00000591885; ENSP00000466867; ENSG00000129667.
GeneID	79651.
KEGG	hsa:79651.
UCSC	uc002jrq.2. human. uc021udh.1. human.
Organism-specific databases
CTD	79651.
GeneCards	GC17M074466.
HGNC	HGNC:20788. RHBDF2.
HPA	HPA018080.
MIM	148500. phenotype. 614404. gene.
neXtProt	NX_Q6PJF5.
Orphanet	2198. Keratosis palmoplantaris - esophageal carcinoma.
PharmGKB	PA134980674.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0705.
HOGENOM	HOG000154118.
HOVERGEN	HBG059673.
InParanoid	Q6PJF5.
OMA	IRKGAAQ.
OrthoDB	EOG4CVG67.
Gene expression databases
Bgee	Q6PJF5.
CleanEx	HS_RHBDF2.
Genevestigator	Q6PJF5.
Family and domain databases
InterPro	IPR002610. Peptidase_S54_rhomboid. IPR022764. Peptidase_S54_rhomboid_dom. IPR022241. Rhomboid_SP. [Graphical view]
PANTHER	PTHR22936. PTHR22936. 1 hit.
Pfam	PF01694. Rhomboid. 1 hit. PF12595. Rhomboid_SP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	79651.
NextBio	68812.
SOURCE	Search...

Entry information

Entry name

RHDF2_HUMAN

Accession

Primary (citable) accession number: Q6PJF5
Secondary accession number(s): A6NEM3 , A8K801, Q5U607, Q5YGQ8, Q9H6E9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 2008
Last sequence update:	July 1, 2008
Last modified:	May 1, 2013
This is version 77 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.