Q15011 (HERP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein

Alternative name(s):
Methyl methanesulfonate (MMF)-inducible fragment protein 1

Gene names

Name:	HERPUD1
Synonyms:	HERP, KIAA0025, MIF1

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	391 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of the endoplasmic reticulum quality control (ERQC) system also called ER-associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins. Could enhance presenilin-mediated beta-amyloid protein 40 generation. Ref.9
Subunit structure	Interacts with PSEN1 and PSEN2. Interacts with SYVN1 and UBXN6. Ref.7 Ref.9 Ref.11
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.1.
Tissue specificity	Widely expressed; in the brain, expression seems to be restricted to neurons and vascular smooth muscle cells. Present in activated microglia in senile plaques in the brain of patients with Alzheimer disease.
Induction	Up-regulated by endoplasmic reticulum stress and CREB3. Ref.1 Ref.10
Miscellaneous	Although the precise topology is not known, experimental data suggest that both the N- and C-termini face the cytosol.
Sequence similarities	Contains 1 ubiquitin-like domain.

Ontologies

Keywords
Biological process	Unfolded protein response
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of signaling protein activity involved in unfolded protein response Traceable author statement. Source: Reactome cellular calcium ion homeostasis Inferred from electronic annotation. Source: Compara negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of protein binding Inferred from electronic annotation. Source: Compara regulation of protein ubiquitination Inferred from electronic annotation. Source: Compara ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: Compara
Cellular_component	endoplasmic reticulum membrane Inferred from direct assay Ref.1. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Experimental confirmation may be lacking for some isoforms.

Isoform 1 (identifier: Q15011-1)

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: Q15011-2)

The sequence of this isoform differs from the canonical sequence as follows:
     76-76: Missing.

Isoform 3 (identifier: Q15011-3)

The sequence of this isoform differs from the canonical sequence as follows:
     76-76: Missing.
     145-302: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 391

391

Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein

PRO_0000114920

Regions

Topological domain

1 – 263

263

Cytoplasmic Potential

Transmembrane

264 – 284

21

Helical; Potential

Topological domain

285 – 289

5

Lumenal Potential

Transmembrane

290 – 310

21

Helical; Potential

Topological domain

311 – 391

81

Cytoplasmic Potential

Domain

10 – 72

63

Ubiquitin-like

Natural variations

Alternative sequence

76

1

Missing in isoform 2 and isoform 3.

VSP_006708

Alternative sequence

145 – 302

158

Missing in isoform 3.

VSP_006709

Natural variant

50

1

R → H.
Corresponds to variant rs2217332 [ dbSNP | Ensembl ].

VAR_024277

Secondary structure

1

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391

Helix Strand Turn

Details...

Beta strand

11 – 15

5

Beta strand

17 – 20

4

Beta strand

24 – 27

4

Helix

34 – 44

11

Turn

51 – 53

3

Beta strand

55 – 58

4

Beta strand

65 – 67

3

Helix

69 – 72

4

Beta strand

75 – 77

3

Beta strand

79 – 85

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 3CA827DC7EF0ED22	FASTA	391	43,720
	10 20 30 40 50 60 MESETEPEPV TLLVKSPNQR HRDLELSGDR GWSVGHLKAH LSRVYPERPR PEDQRLIYSG 70 80 90 100 110 120 KLLLDHQCLR DLLPKQEKRH VLHLVCNVKS PSKMPEINAK VAESTEEPAG SNRGQYPEDS 130 140 150 160 170 180 SSDGLRQREV LRNLSSPGWE NISRPEAAQQ AFQGLGPGFS GYTPYGWLQL SWFQQIYARQ 190 200 210 220 230 240 YYMQYLAATA ASGAFVPPPS AQEIPVVSAP APAPIHNQFP AENQPANQNA APQVVVNPGA 250 260 270 280 290 300 NQNLRMNAQG GPIVEEDDEI NRDWLDWTYS AATFSVFLSI LYFYSSLSRF LMVMGATVVM 310 320 330 340 350 360 YLHHVGWFPF RPRPVQNFPN DGPPPDVVNQ DPNNNLQEGT DPETEDPNHL PPDRDVLDGE 370 380 390 QTSPSFMSTA WLVFKTFFAS LLPEGPPAIA N
	Isoform 2 [UniParc]. Checksum: 7BCA8854403C71AF	FASTA	390	43,592
	10 20 30 40 50 60 MESETEPEPV TLLVKSPNQR HRDLELSGDR GWSVGHLKAH LSRVYPERPR PEDQRLIYSG 70 80 90 100 110 120 KLLLDHQCLR DLLPKEKRHV LHLVCNVKSP SKMPEINAKV AESTEEPAGS NRGQYPEDSS 130 140 150 160 170 180 SDGLRQREVL RNLSSPGWEN ISRPEAAQQA FQGLGPGFSG YTPYGWLQLS WFQQIYARQY 190 200 210 220 230 240 YMQYLAATAA SGAFVPPPSA QEIPVVSAPA PAPIHNQFPA ENQPANQNAA PQVVVNPGAN 250 260 270 280 290 300 QNLRMNAQGG PIVEEDDEIN RDWLDWTYSA ATFSVFLSIL YFYSSLSRFL MVMGATVVMY 310 320 330 340 350 360 LHHVGWFPFR PRPVQNFPND GPPPDVVNQD PNNNLQEGTD PETEDPNHLP PDRDVLDGEQ 370 380 390 TSPSFMSTAW LVFKTFFASL LPEGPPAIAN
	Isoform 3 [UniParc]. Checksum: BE916EB3E3CD79C0	FASTA	232	26,220
	10 20 30 40 50 60 MESETEPEPV TLLVKSPNQR HRDLELSGDR GWSVGHLKAH LSRVYPERPR PEDQRLIYSG 70 80 90 100 110 120 KLLLDHQCLR DLLPKEKRHV LHLVCNVKSP SKMPEINAKV AESTEEPAGS NRGQYPEDSS 130 140 150 160 170 180 SDGLRQREVL RNLSSPGWEN ISRHHVGWFP FRPRPVQNFP NDGPPPDVVN QDPNNNLQEG 190 200 210 220 230 TDPETEDPNH LPPDRDVLDG EQTSPSFMST AWLVFKTFFA SLLPEGPPAI AN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Herp, a new ubiquitin-like membrane protein induced by endoplasmic reticulum stress." Kokame K., Agarwala K.L., Kato H., Miyata T. J. Biol. Chem. 275:32846-32853(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION, SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY. Tissue: Umbilical vein endothelial cell.
[2]	"Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1." Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S., Nagase T., Seki N., Ishikawa K., Tabata S. DNA Res. 1:27-35(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Bone marrow.
[3]	Yu W., Gibbs R.A. Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Brain.
[4]	"Identification of ERSE-II, a new cis-acting element responsible for the ATF6-dependent mammalian unfolded protein response." Kokame K., Kato H., Miyata T. J. Biol. Chem. 276:9199-9205(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"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] (ISOFORMS 1 AND 3). Tissue: Brain, Eye, Placenta and Testis.
[7]	"Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein." Sai X., Kawamura Y., Kokame K., Yamaguchi H., Shiraishi H., Suzuki R., Suzuki T., Kawaichi M., Miyata T., Kitamura T., De Strooper B., Yanagisawa K., Komano H. J. Biol. Chem. 277:12915-12920(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PSEN1 AND PSEN2.
[8]	"The novel MMS-inducible gene Mif1/KIAA0025 is a target of the unfolded protein response pathway." van Laar T., Schouten T., Hoogervorst E., van Eck M., van der Eb A.J., Terleth C. FEBS Lett. 469:123-131(2000) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION. Tissue: Skin fibroblast.
[9]	"The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway." Schulze A., Standera S., Buerger E., Kikkert M., van Voorden S., Wiertz E., Koning F., Kloetzel P.-M., Seeger M. J. Mol. Biol. 354:1021-1027(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH SYVN1.
[10]	"Luman/CREB3 induces transcription of the endoplasmic reticulum (ER) stress response protein Herp through an ER stress response element." Liang G., Audas T.E., Li Y., Cockram G.P., Dean J.D., Martyn A.C., Kokame K., Lu R. Mol. Cell. Biol. 26:7999-8010(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[11]	"Ubxd1 is a novel co-factor of the human p97 ATPase." Madsen L., Andersen K.M., Prag S., Moos T., Semple C.A., Seeger M., Hartmann-Petersen R. Int. J. Biochem. Cell Biol. 40:2927-2942(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH UBXN6.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"Solution structure of the UBL-domain of HERP." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2004) to the PDB data bank Cited for: STRUCTURE BY NMR OF 10-90.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB034989 mRNA. Translation: BAB07891.1.
D14695 mRNA. Translation: BAA03521.1.
AF055001 mRNA. Translation: AAC09355.1.
AF055003 mRNA. Translation: AAC09357.1.
AB034990 Genomic DNA. Translation: BAB19010.1.
CR457116 mRNA. Translation: CAG33397.1.
BC000086 mRNA. Translation: AAH00086.1.
BC008320 mRNA. Translation: AAH08320.1.
BC009739 mRNA. Translation: AAH09739.1.
BC032673 mRNA. Translation: AAH32673.1.

IPI

IPI00014171.
IPI00179347.
IPI00219266.

RefSeq

NP_001010989.1. NM_001010989.2.
NP_001010990.1. NM_001010990.1.
NP_055500.1. NM_014685.3.

UniGene

Hs.146393.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WGD	NMR	-	A	10-90	[»]

ProteinModelPortal

Q15011.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-46662N.

IntAct

Q15011. 8 interactions.

MINT

MINT-2867283.

STRING

9606.ENSP00000300302.

PTM databases

PhosphoSite

Q15011.

Polymorphism databases

DMDM

3123034.

Proteomic databases

PaxDb

Q15011.

PRIDE

Q15011.

Protocols and materials databases

DNASU

9709.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000300302; ENSP00000300302; ENSG00000051108.
ENST00000344114; ENSP00000340931; ENSG00000051108.
ENST00000439977; ENSP00000409555; ENSG00000051108.

GeneID

9709.

KEGG

hsa:9709.

UCSC

uc002eke.1. human.
uc002ekf.1. human.
uc010ccp.1. human.

Organism-specific databases

CTD

9709.

GeneCards

GC16P056965.

HGNC

HGNC:13744. HERPUD1.

HPA

CAB037041.
CAB037104.
HPA040754.
HPA041219.

MIM

608070. gene.

neXtProt

NX_Q15011.

PharmGKB

PA29252.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG259558.

HOGENOM

HOG000252989.

HOVERGEN

HBG051899.

InParanoid

Q15011.

KO

K14027.

OMA

NFPNDGP.

OrthoDB

EOG4KKZ3C.

PhylomeDB

Q15011.

Enzyme and pathway databases

Reactome

REACT_116125. Disease.

Gene expression databases

ArrayExpress

Q15011.

Bgee

Q15011.

CleanEx

HS_HERPUD1.

Genevestigator

Q15011.

GermOnline

ENSG00000051108. Homo sapiens.

Family and domain databases

InterPro

IPR000626. Ubiquitin.
IPR019955. Ubiquitin_supergroup.
[Graphical view]

Pfam

PF00240. ubiquitin. 1 hit.
[Graphical view]

SMART

SM00213. UBQ. 1 hit.
[Graphical view]

PROSITE

PS50053. UBIQUITIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

HERPUD1. human.

EvolutionaryTrace

Q15011.

GenomeRNAi

9709.

NextBio

36487.

SOURCE

Search...

Entry information

Entry name

HERP1_HUMAN

Accession

Primary (citable) accession number: Q15011
Secondary accession number(s): O60644, Q6IAN8, Q96D92

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 125 of the entry and version 1 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.