O75146 (HIP1R_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Huntingtin-interacting protein 1-related protein
Short name=HIP1-related protein

Alternative name(s):
Huntingtin-interacting protein 12
Short name=HIP-12

Gene names

Name:	HIP1R
Synonyms:	HIP12, KIAA0655

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	1068 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of clathrin-coated pits and vesicles, that may link the endocytic machinery to the actin cytoskeleton. Binds 3-phosphoinositides (via ENTH domain). May act through the ENTH domain to promote cell survival by stabilizing receptor tyrosine kinases following ligand-induced endocytosis. Ref.5 Ref.6
Subunit structure	Interacts with actin. Does not interact with huntingtin By similarity. Interacts with CLTB and HIP1. Homodimer. Homodimerization promotes actin binding. Ref.5 Ref.7 Ref.11
Subcellular location	Cytoplasm › perinuclear region. Endomembrane system. Cytoplasmic vesicle › clathrin-coated vesicle membrane. Note: Membrane-associated protein, mainly localized at the endocytic compartments and in the perinuclear region. Ref.5 Ref.6
Tissue specificity	Brain, heart, kidney, pancreas, and liver, but not in lung or placenta.
Domain	Binds F-actin via the talin-like I/LWEQ domain.
Sequence similarities	Belongs to the SLA2 family. Contains 1 ENTH (epsin N-terminal homology) domain. Contains 1 I/LWEQ domain.
Sequence caution	The sequence BAA31630.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Endocytosis
Cellular component	Cytoplasm Cytoplasmic vesicle Membrane
Coding sequence diversity	Polymorphism
Domain	Coiled coil
Ligand	Actin-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	receptor-mediated endocytosis Inferred from mutant phenotype Ref.5. Source: UniProtKB
Cellular_component	clathrin-coated vesicle Inferred from direct assay Ref.5Ref.6. Source: UniProtKB clathrin-coated vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell coated pit Non-traceable author statement. Source: UniProtKB cytoskeleton Inferred from electronic annotation. Source: Compara perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	actin binding Non-traceable author statement. Source: UniProtKB phosphatidylinositol binding Inferred from direct assay Ref.6. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1068

1068

Huntingtin-interacting protein 1-related protein

PRO_0000083984

Regions

Domain

23 – 151

129

ENTH

Domain

771 – 1012

242

I/LWEQ

Region

867 – 924

58

Important for actin binding

Coiled coil

347 – 599

253

Potential

Amino acid modifications

Modified residue

1017

1

Phosphoserine Ref.8

Natural variations

Natural variant

404

1

K → Q.
Corresponds to variant rs7972242 [ dbSNP | Ensembl ].

VAR_051029

Natural variant

516

1

K → Q.
Corresponds to variant rs7972242 [ dbSNP | Ensembl ].

VAR_051030

Natural variant

782

1

V → M.
Corresponds to variant rs2271051 [ dbSNP | Ensembl ].

VAR_020043

Natural variant

943

1

N → S.
Corresponds to variant rs3736414 [ dbSNP | Ensembl ].

VAR_051031

Experimental info

Mutagenesis

867

1

R → D: Reduced acting binding. Ref.11

Mutagenesis

871

1

G → D: Reduced acting binding. Ref.11

Mutagenesis

875

1

A → D: Reduced acting binding. Ref.11

Mutagenesis

922 – 924

3

KVK → DDD: Strongly reduced actin binding. Ref.11

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1068

Helix Strand Turn

Details...

Helix

776 – 778

3

Helix

779 – 811

33

Helix

814 – 852

39

Helix

858 – 864

7

Helix

866 – 895

30

Helix

900 – 922

23

Turn

929 – 931

3

Helix

932 – 964

33

Sequences

	Sequence		Length	Mass (Da)
	O75146 [UniParc]. Last modified April 27, 2001. Version 2. Checksum: 3CBC7CF1191BFF8F	FASTA	1,068	119,388
	10 20 30 40 50 60 MNSIKNVPAR VLSRRPGHSL EAEREQFDKT QAISISKAIN TQEAPVKEKH ARRIILGTHH 70 80 90 100 110 120 EKGAFTFWSY AIGLPLPSSS ILSWKFCHVL HKVLRDGHPN VLHDCQRYRS NIREIGDLWG 130 140 150 160 170 180 HLHDRYGQLV NVYTKLLLTK ISFHLKHPQF PAGLEVTDEV LEKAAGTDVN NIFQLTVEMF 190 200 210 220 230 240 DYMDCELKLS ESVFRQLNTA IAVSQMSSGQ CRLAPLIQVI QDCSHLYHYT VKLLFKLHSC 250 260 270 280 290 300 LPADTLQGHR DRFHEQFHSL RNFFRRASDM LYFKRLIQIP RLPEGPPNFL RASALAEHIK 310 320 330 340 350 360 PVVVIPEEAP EDEEPENLIE ISTGPPAGEP VVVADLFDQT FGPPNGSVKD DRDLQIESLK 370 380 390 400 410 420 REVEMLRSEL EKIKLEAQRY IAQLKSQVNA LEGELEEQRK QKQKALVDNE QLRHELAQLR 430 440 450 460 470 480 AAQLEGERSQ GLREEAERKA SATEARYNKL KEKHSELVHV HAELLRKNAD TAKQLTVTQQ 490 500 510 520 530 540 SQEEVARVKE QLAFQVEQVK RESELKLEEK SDQLEKLKRE LEAKAGELAR AQEALSHTEQ 550 560 570 580 590 600 SKSELSSRLD TLSAEKDALS GAVRQREADL LAAQSLVRET EAALSREQQR SSQEQGELQG 610 620 630 640 650 660 RLAERESQEQ GLRQRLLDEQ FAVLRGAAAE AAGILQDAVS KLDDPLHLRC TSSPDYLVSR 670 680 690 700 710 720 AQEALDAVST LEEGHAQYLT SLADASALVA ALTRFSHLAA DTIINGGATS HLAPTDPADR 730 740 750 760 770 780 LIDTCRECGA RALELMGQLQ DQQALRHMQA SLVRTPLQGI LQLGQELKPK SLDVRQEELG 790 800 810 820 830 840 AVVDKEMAAT SAAIEDAVRR IEDMMNQARH ASSGVKLEVN ERILNSCTDL MKAIRLLVTT 850 860 870 880 890 900 STSLQKEIVE SGRGAATQQE FYAKNSRWTE GLISASKAVG WGATQLVEAA DKVVLHTGKY 910 920 930 940 950 960 EELIVCSHEI AASTAQLVAA SKVKANKHSP HLSRLQECSR TVNERAANVV ASTKSGQEQI 970 980 990 1000 1010 1020 EDRDTMDFSG LSLIKLKKQE METQVRVLEL EKTLEAERMR LGELRKQHYV LAGASGSPGE 1030 1040 1050 1060 EVAIRPSTAP RSVTTKKPPL AQKPSVAPRQ DHQLDKKDGI YPAQLVNY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"HIP12 is a non-proapoptotic member of a gene family including HIP1, an interacting protein with huntingtin." Chopra V.S., Metzler M., Rasper D.M., Engqvist-Goldstein A.E.Y., Singaraja R., Gan L., Fichter K.M., McCutcheon K., Drubin D., Nicholson D.W., Hayden M.R. Mamm. Genome 11:1006-1015(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:169-176(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Cloning, expression analysis, and chromosomal localization of HIP1R, an isolog of huntingtin interacting protein (HIP1)." Seki N., Muramatsu M., Sugano S., Suzuki Y., Nakagawara A., Ohhira M., Hayashi A., Hori T., Saito T. J. Hum. Genet. 43:268-271(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 179-1068. Tissue: Neuroblastoma.
[5]	"HIP1 and HIP12 display differential binding to F-actin, AP2, and clathrin. Identification of a novel interaction with clathrin light chain." Legendre-Guillemin V., Metzler M., Charbonneau M., Gan L., Chopra V., Philie J., Hayden M.R., McPherson P.S. J. Biol. Chem. 277:19897-19904(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CLTB AND HIP1, SUBCELLULAR LOCATION.
[6]	"HIP1 and HIP1r stabilize receptor tyrosine kinases and bind 3-phosphoinositides via epsin N-terminal homology domains." Hyun T.S., Rao D.S., Saint-Dic D., Michael L.E., Kumar P.D., Bradley S.V., Mizukami I.F., Oravecz-Wilson K.I., Ross T.S. J. Biol. Chem. 279:14294-14306(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[7]	"Huntingtin-interacting protein 1 (Hip1) and Hip1-related protein (Hip1R) bind the conserved sequence of clathrin light chains and thereby influence clathrin assembly in vitro and actin distribution in vivo." Chen C.-Y., Brodsky F.M. J. Biol. Chem. 280:6109-6117(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CLTB.
[8]	"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-1017, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[10]	"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].
[11]	"Structural definition of the F-actin-binding THATCH domain from HIP1R." Brett T.J., Legendre-Guillemin V., McPherson P.S., Fremont D.H. Nat. Struct. Mol. Biol. 13:121-130(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 771-971, PARTIAL PROTEIN SEQUENCE, MASS SPECTROMETRY, SUBUNIT, MUTAGENESIS OF ARG-867; GLY-871; ALA-875 AND 922-LYS--LYS-924.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB014555 mRNA. Translation: BAA31630.1. Different initiation.
AC027290 Genomic DNA. No translation available.
AB013384 mRNA. Translation: BAA33713.1.

IPI

IPI00024417.

RefSeq

NP_003950.1. NM_003959.1.

UniGene

Hs.524815.
Hs.714965.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1R0D	X-ray	1.90	A/B/D/E/F/G/H/I	771-971	[»]

ProteinModelPortal

O75146.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-17042N.

IntAct

O75146. 1 interaction.

MINT

MINT-2797489.

STRING

9606.ENSP00000253083.

PTM databases

PhosphoSite

O75146.

Proteomic databases

PaxDb

O75146.

PRIDE

O75146.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000253083; ENSP00000253083; ENSG00000130787.

GeneID

9026.

KEGG

hsa:9026.

UCSC

uc001udi.1. human.

Organism-specific databases

CTD

9026.

GeneCards

GC12P123319.

HGNC

HGNC:18415. HIP1R.

HPA

CAB017187.

MIM

605613. gene.

neXtProt

NX_O75146.

PharmGKB

PA128394543.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG280957.

HOGENOM

HOG000020612.

HOVERGEN

HBG005968.

InParanoid

O75146.

OMA

SESVFRQ.

Enzyme and pathway databases

Reactome

REACT_11123. Membrane Trafficking.

Gene expression databases

ArrayExpress

O75146.

Bgee

O75146.

CleanEx

HS_HIP1R.

Genevestigator

O75146.

Family and domain databases

Gene3D

1.25.40.90. 1 hit.

InterPro

IPR011417. ANTH_dom.
IPR008942. ENTH_VHS.
IPR013809. Epsin-like_N.
IPR002558. ILWEQ_dom.
[Graphical view]

Pfam

PF07651. ANTH. 1 hit.
PF01608. I_LWEQ. 1 hit.
[Graphical view]

ProDom

PD011820. ILWEQ. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00273. ENTH. 1 hit.
SM00307. ILWEQ. 1 hit.
[Graphical view]

SUPFAM

SSF48464. ENTH_VHS. 1 hit.

PROSITE

PS50942. ENTH. 1 hit.
PS50945. I_LWEQ. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

HIP1R. human.

EvolutionaryTrace

O75146.

GenomeRNAi

9026.

NextBio

33819.

SOURCE

Search...

Entry information

Entry name

HIP1R_HUMAN

Accession

Primary (citable) accession number: O75146
Secondary accession number(s): A6NHQ6, Q9UED9

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	April 27, 2001
Last modified:	May 1, 2013
This is version 117 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.